References, Anti-Aging Medicine Articles, Books, Journals & Patents

6. Insulin Utilization and Aging
____[(6), Index/Insulin, Diabetes; LEF, Links, Images, Papers, Patents, Books, Amazon, Wikipedia/Insulin].

7. Hayflick Limit Theory of Aging Based on Telomeres [(7), Links, Images, Papers, Patents, Books].
See also TA Sciences Science Library.

Jerry W. Shay and Woodring E. Wright (2000),
Hayflick, his limit, and cellular ageing,
Nature/Reviews/Molecular Cell Biology, October, 2000.
Shows microphotographs of the difference between young and old human fibroblast [Books] diploid cells (strain WI-38).

Carrel, A. (1912),
On the permanent life of tissues outside of the organism,
Journal of Experimental Medicine, 1912, 15: 516-527.
Hayflick had to contend with Nobelist Carrel concerning limits to cell division in vitro.

Harry Eagle (1955),
Nutrition Needs of Mammalian Cells in Tissue Culture,
Science 122: 1955, pp. 501-504.
The medium developed by Eagle is still the basic medium used for animal cell culture.

H. Earle Swim and Robert F. Parker (1957),
CULTURE CHARACTERISTICS OF HUMAN FIBROBLASTS PROPAGATED SERIALLY,
American Journal of Epidemiology, 1957, Volume 66, Number 2 Pp. 235-243, including 24 references with titles and historic micophotos.
[Papers]. This paper, which includes some good microphotos of non-senescent and senescent cells, seems to be one of the first to have detected limits to the division of human foreskin fibroblasts in culture at the 49th passage, a topic reviewed again by Hayflick and Moorhead in 1961. A few of Swim and Parker's fibroblasts from 2 (uterine and foreskin fibroblast) of ten strains and 51 cultures examined seem to have escaped in morphologically transformed and immortalized condition (resembling that of malignant cells) as strains U12-705 and FS4-705, still dividing after 3 years at the time of publication. Normal cultures invariably stopped propagating after 2 to 12 months of active growth. It was noted in a separate paper (Haff and Swim, 1956) that rabbit fibroblasts sometimes escaped as immortal cells without morphological transformation corresponding to a malignant phenotype. Swim and Parker were looking for media that would keep fibroblast cultures propagating indefinitely, but photographed two young fibroblast cultures (of uterine and foreskin fibroblasts) after a few weeks and compared them to the senescent fibroblasts obtained from the same cells grown in their better media after a year and 40 passages (uterine) or 49 passages (foreskin), each passage corresponding to a cell number doubling. Signs of morphological transformations corresponding to senescent cells were especially evident in their photo of foreskin fibroblasts at 49 cell divisions. Foreskin fibroblasts divided more vigorously and for a longer period than fibroblasts obtained from 10 other tissues. Media featuring normal horse serum supported fibroblasts better than media featuring human serum or bovine serum. Media containing 5% beef embryo extract and 10 to 20 per cent horse serum worked best, and many different media combinations were tested. H. Earle Swim and Robert F. Parker worked at the Department of Microbiology, Western Reserve University, School of Medicine, in Cleveland, Ohio.

Leonard Hayflick and Moorehead PS (1961),
Serial Cultivation of human diploid cell strains, Exp Cell Res. 25:585-621, including 35 references without titles, and no photos.
"Cell strains (of non-transformed fibroblasts)...degenerate after about 50 subcultivations and 1 year in culture....the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level." (italics mine). Hayflick and Moorehead define "cell strains" as cultures of morphologically unaltered cells and "cell lines" as cultures of morphologically transformed cells, which may feature heteroploid characteristics and immortalized cellular propagation. The article emanated from the "Wistnr" Institute of Anatomy and Biology, Philadelphia, Pennsylvania. This paper was anticipated in most respects by the prior research of Swim and Parker in 1957.

JD Watson (1972),
Origin of concatemeric T7 DNA,
Nature New Biology, 239:197-201, 1972.
The key initial paper in the end-replication problem [Links, Books, Papers, Images, Amazon/the telomere end-replication problem] involving Okazaki fragments in DNA lagging strand synthesis and RNA primers. Leads to a consideration of incomplete copying of template margin in enzymic synthesis of polynucleotides as developed by Alexey Olovnikov for application to cellular age timekeeping.

AM Olovnikov (1973),
A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon as a cellular clock.,
Journal of Theoretical Biology, Sep 14,1973;41(1):181-90.

Elizabeth Blackburn, Joseph G Gall [Links] (1978),
A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena,
Journal of Molecular Biology 1978 Mar 25;120(1):33-53. (Discovery of the telomere.)

Greider CW and Blackburn EH (1985),
Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. (Discovery of telomerase),
Cell 43:405-13.

Cooke HJ, Smith BA (1986),
Variability at the telomeres of the human X/Y pseudoautosomal region,
Cold Spring Harbor Symposium for Quantitative Biology 1986;51 Pt 1:213-219.
Cooke and Smith reported that telomeres are longer in reproductive haploid cells such as spermatazoa and egg cells but shorten with age in other somatic cells.

Moyzis RK, Buckingham JM, Cram LS, Dani M, LL (1988),
A Highly Conserved Repetitive DNA Sequence,(TTAGGG)_n, present at the Telomeres of Human Chromosomes,
Proc Natl Acad Sci. 85(18): 6622-6626.

Wright WE, Shay JW, Pereira-Smith OM (1989),
Reversible Cellular Senescence: implications for immortalization of normal human diploid fibroblasts,
Mol Cell Biol, 9(7): 3088-3092.

Morin, G. B. (1989),
The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats,
Cell 59:521-529.

CB Harley, Futcher, and Greider (1990),
Telomeres shorten during aging of human fibroblasts,
Nature 345: 458-460.

Shay, J.W., Pereira-Smith, O.M., and Wright, W.E. (1991),
A role for both Rb and p53 in the regulation of human cellular senescence,
Experimental Cell Research, 196, 33-39.

Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Baccetti S (1992),
Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity,
EMBO Journal 1992, 11:192-1929.

Richard C. Allsopp, H Vaziri, C Patterson, S. Goldstein, E. V. Younglai, A Bruce Futcher, Carol W. Greider and Calvin B. Harley (1992),
Telomere Length Predicts Replicative Capacity of Human Fibroblasts,
Proc. Natl. Acad. Sci. USA, vol. 89, November 1992.

Counter, C. M., A. A. Avilion, C. E. LeFeuvre, N. G. Stewart, C. W. Greider, C. B. Harley, and S. Bacchetti (1992),
Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity,
EMBO Journal, 11:1921-1929.

West, MD (1994),
The cellular and molecular biology of skin aging,
Archives of Dermatology, 1994 130(1) 87-95.

Richard C. Allsopp, Edwin Chang, Mohammad Kashefi-Aazam, Evgeny I. Rogaev,
Mieczyslaw A. Piatyszek, Jerry W. Shay and Calvin B. Harley (1995),
Telomere Shortening Is Associated with Cell Division in Vitro and in Vivo,
Experimental Cell Research, Volume 220, Issue 1, September 1995, Pages 194-200.

RC Allsopp, E Chang, M Kashefi-Aazam, EI Rogaev, (1995),
Telomere shortening is associated with cell division in vitro and in vivo.,
Experimental Cell Research, 1995.

Allsopp, R. C., and C. B. Harley (1995),
Evidence for a critical telomere length in senescent human fibroblasts,
Experimental Cell Research, 219:130-136.

Scott Henderson, Richard Allsopp, David Spector, Sy-Shi Wang, Calvin Harley (1996),
In Situ Analysis of Changes in Telomere Size during Replicative Aging and Cell Transformation,
Journal of Cell Biology, Volume 134, 1996, pp 1-12.

Atadja, P., Wong, H., Garkavtsev, L., Veillette, C., and Riabowol, K. (1995),
Increased activity of p53 in senescing fibroblasts,
Proceedings of the National Academy of Science USA, 92, 3848-8352.

Hara, E., Tsuri, H, Sinozaki, S., and Oda, K. (1996),
Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of lifespan in human diploid fibroblasts,
Biochemistry and Biophysics Research Communications, 179, 528-534.

Lansdorp, P.M., Verwoerd, N.P., van de Rijke, F.M., Dragowska, V.,
Little, M.T., Dirks, R.W., Raap, A.K., and Tanke, H.J. (1996),
Heterogeneity in telomere length of human chromosomes,
Human Molecular Genetics 5: 685-691.

Alcorta, D.A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., and Barrett, J.C. (1996),
Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative sensescence of normal human fibroblasts,
Proceedings of the National Academy of Sciences USA, 93, 13742-13747.

Wright, W.E., V.M.Tesmer, K.E.Huffman, S.D.Levene, and J.W.Shay (1997),
Normal human chromosomes have long G-rich telomeric overhangs at one end,
Genes and Development 11: 2801-2809.

Thomas R. Cech et al, (1997),
(Geron Patent) Telomerase, US Patent 6093809.

Calvin B. Harley (1997),
Human Aging and Telomeres,
Ciba Found Symposium 1997;211:129-39; discussion 139-44. [Papers].

CP Chiu and CB Harley (1997),
Replicative senescence and cell immortality: the role of telomeres and telomerase,
Proceedings of the Society for Experimental Biology and Medicine, Vol 214, 99-106. [Links, Images, Papers, Patents, Books].

Serrano, M., Lin, A.W., McCurrach, M.E., Beach, D., and Lowe, S.W. (1997),
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a,
Cell 88, 593-602. [Index/p16, Index/p53,
Links/premature cell senescence associated with accumulation of p16INK4a, Images, Papers, Patents, Books,
Links/premature cell senescence associated with accumulation of p53, Images, Papers, Patents, Books].

Gire, V., and Wynford-Thomas, D. (1998),
Reinitiation of DNA synthesis and cell division in senescent human fibroblasts by microinjection of anti-p53 antibodies,
Mol. Cell Biol. 18, 1611-1621.

Kiyono,T., Foster, S.A., Koop, J.I., McDougall, J.K., Galloway, D.A., and Klingelhutz, A.J. (1998),
Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells,
Nature 396, 84-88.

Nugent, C.I., and Lundblad, V. (1998),
The telomerase reverse transcriptase: components and regulation,
Genes and Development 12: 1073-1085.

Andrea G. Bodnar, Michel Ouellette, Maria Frolkis, Shawn E. Holt, Choy-Pik Chiu, Gregg B. Morin,
Calvin B. Harley, Jerry W. Shay, Serge Lichtsteiner, Woodring E. Wright (1998),
Extension of life-span by introduction of telomerase into normal human cells,
Science 16 January 1998, pp. 349 - 352.

Homayoun Vaziri and Samuel Benchimol (1998),
Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span,
Current Biology 8, 5: 26 Feb 1998, 279-282.

Counter, C. M., M. Meyerson, E. N. Eaton, L. W. Ellisen, S. D. Caddle, D. A. Haber, and R. A. Weinberg (1998),
Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase,
Oncogene, 16:1217-1222.

Vaziri, H., and S. Benchimol (1998),
Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span,
Curr. Biol, 8:279-282.

Shawn E. Holt, Dara L. Aisner, Joseph Baur, Valerie M. Tesmer, Marife Dy, Michel Oullette, James B. Trager,
Gregg B. Morin, David O. Toft, Jerry W. Shay, Woodring E. Wright, and Michael A. White (1999),
Functional requirement of p23 and Hsp90 in telomerase complexes,
Genes and Development 1999 13: 817-826.

Herbert, B., A.E.Pitts, S.I.Baker, S.E.Hamilton, W.E. Wright, J.W.Shay, and D.R. Corey (1999),
Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death,
Proc. Natl. Acad. Sci. USA 96:14276-14281.

Brehm, A., and Kouzarides, T. (1999),
Retinoblastoma protein meets chromatin,
Trends in Biochemical Sciences 24, 142-145.

Stein, G.H., Drullinger L.F., Soulard, A., Dulic, V. (1999),
Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts,
Mol.Cell.Biol., 19, 2109-2117.

Ducray C., Pommier, J.P., Martins, L., Boussin, F.D., and Sabatier, L (1999),
Telomere dynamics, end-to-end-fusions and telomerase activation during the human fibroblast immortalization process,
Oncogene, 18, 4211-4223.

David Stipp (1999),
The Hunt For The Youth Pill From cell-immortalizing drugs to cloned organs, biotech finds new ways to fight against time's toll. Fortune, October 11, 1999. (TA Sciences: TA-65). Green suggests astragalus extracts, plenty, with perseverance [81s].

Carmela P. Morales, Shawn E. Holt, Michel Ouellette, Kiran J. Kaur, Ying Yan, Kathleen S. Wilson, Michael A. White, Woodring E. Wright & Jerry W. Shay, (1999),
Absence of cancer−associated changes in human fibroblasts immortalized with telomerase,
Nature Genetics 21, 115 - 118 (1999).

Griffith, Comeau, and Rosenfield (1999),
Mammalian Telomeres end in a Large Duplex Loop,
Cell 97: 503-514.

M. A. Blasco, Susan M. Gasser, and Joachim Lingner, (1999),
Telomeres and telomerase,
Genes and Development, Vol. 13, No. 18, pp. 2353-2359, September 15, 1999.

Carol W. Greider (1999),
Telomeres Do D-Loop T-Loop Minireview.

Jerry W. Shay (1999),
On telomeric t-loops and d-loops.

Actually, this was Jerry W. Shay (1999). At the end of the millenium, a view of the end, Nature Genetics, 23, 382-383 (1999).

Kami Ahmada and Kent G. Golica (1999),
Telomere Loss in Somatic Cells of Drosophila Causes Cell Cycle Arrest and Apoptosis,
Genetics, Vol. 151, 1041-1051, March 1999.

Carmela P. Morales, Shawn E. Holt, Michel Ouellette, Kiran J. Kaur, Ying Yan, Kathleen S. Wilson, Michael A. White, Woodring E. Wright & Jerry W. Shay (1999),
Absence of cancer−associated changes in human fibroblasts immortalized with telomerase,
Nature Genetics 21, 115 - 118 (1999).

Izumi Horikawa, P. LouAnn Cable, Cynthia Afshari and J. Carl Barrett (1999),
Cloning and Characterization of the Promoter Region of Human Telomerase Reverse Transcriptase Gene,
Cancer Research, 59, 826-830, February 1, 1999 [Papers, Books].

Herbert, B., A. E. Pitts, S. I. Baker, S. E. Hamilton, W. E. Wright, J. W. Shay, and D. R. Corey (1999),
Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death,
Proc. Natl. Acad. Sci, USA 96:14276-14281.

Bryce LA, et al., (2000),
Mapping the gene for human telomerase reverse transcriptase, hTERT, to chromosome 5p15.33 by fluorescence in situ hybridization,
Neoplasia, 2000.

S. Marcand, V. Brevet, C. Mann, and E. Gilson (2000),
Cell cycle restriction of telomere elongation,
Current Biology 10, 487-490.

WD Funk, CK Wang, DN Shelton, CB Harley, GD Pagon, et al., (2000),
Telomerase Expression Restores Dermal Integrity to in Vitro-Aged Fibroblasts in a Reconstituted Skin Model, Experimental Cell Research, Volume 258, Number 2, August 2000 , pp. 270-278(9).

DG Farwell, KA Shera, JI Koop, GA Bonnet, et al., (2000),
Genetic and Epigenetic Changes in Human Epithelial Cells Immortalized by Telomerase,
American Journal of Pathology, 2000;156:1537-1547.

Yong-Ouk You, Gene Lee and Byung-Moo Min, (2000),
Retinoic Acid Extends the in Vitro Life Span of Normal Human Oral Keratinocytes by Decreasing p16INK4A Expression and Maintaining Telomerase Activity,
Biochemical and Biophysical Research Communications, Volume 268, Issue 2, 16 February 2000, Pages 268-274.
Bailey, S.M., Cornforth, M.N., Kurimasa, A., Chen, D.J., and Goodwin, E.H., (2001),
Strand-specific postreplicative processing of mammalian telomeres,
Science 293: 2462-2465.

Baur, J.A., Zou, Y., Shay, J.W., and Wright, W.E. (2001),
Telomere position effect in human cells,
Science 292, 2075.

J.L. Munoz-Jordan, G.A. Cross, T. de Lange, and J. D. Griffith (2001),
T-loops at typanosome telomeres,
EMBO Journal 20, 579-588.

Blackburn, Elizabeth, (2001),
Switching and signaling at the telomere,
Cell, Vol. 106, 661-673, September 21, 2001.

Ali Ahmed, MD, MPH, and Trygve Tollefsbol, PhD (2001),
Telomeres and Telomerase: Basic Science Implications for Aging,
Journal of the American Geriatrics Society, Volume 49 Issue 8 Page 1105-1109, August 2001.

Campisi, J., Kim, S., Lim, C., and Rubio, M. (2001),
Cellular senescence, cancer, and aging: The telomere connection,
Experimental Gerontology, 36, 1619-1637.

Itahana, K., Dimri, G., and Campisi, J. (2001),
Regulation of cellular senescence by p53,
European Journal of Biochemistry, 268, 2784-2791.

Rheinwald, J.G., et al. (2002),
A two-stage, p16(INK4a)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status,
Mol. Cell. Biol., 22, 5157-5172.

N. R. Forsyth, W. E. Wright, J. W. Shay (2002),
Telomerase and differentiation in multicellular organisms: Turn it off, turn it on, and turn it off again,
Differentiation, Volume 69 Issue 4-5 Page 188-197, January 2002.

Robert F. Newbold, (2002),
The significance of telomerase activation and cellular immortalization in human cancer,
Mutagenesis, Vol. 17, No. 6, 539-550, November 2002.

Yu-Sheng Cong, Woodring E. Wright, and Jerry W. Shay (2002),
Human Telomerase and Its Regulation,
Microbiology and Molecular Biology Reviews, Sept. 2002.

Karlsreder, J., Smogorzewska, A., and de Lange, T. (2002),
Senescence induced by altered telomere state, not telomere loss,
Science 295, 446-2449.

Ithana,K., et al. (2003),
Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1,
Mol Cell. Biol., 23, 389-401.

Nicholas R. Forsyth, A. Patrice Evans, Jerry W. Shay and Woodring E. Wright (2003),
Developmental differences in the immortalization of lung fibroblasts by telomerase,
Aging Cell: 2 (5), 235-243.

RC Allsopp, GB Morin, R DePinho, CB Harley, (2003),
Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation,
Blood, 15 July 2003, vol. 102, no. 2. pp. 517-520. HSCs are hemopoietic stem cells.

Silvia Di Donna, Kamel Mamchaoui, Racquel N. Cooper, Sophie Seigneurin-Venin, Jacques Tremblay, Gillian S. Butler-Browne and Vincent Mouly (2003),
Telomerase Can Extend the Proliferative Capacity of Human Myoblasts, but Does Not Lead to Their Immortalization,
Molecular Cancer Research 1:643-653.

RM Cawthon, KR Smith, E O'Brien, A Sivatchenko, RA, et al. (2003),
Association Between Telomere Length in blood and mortality in people aged 60 years or older,
(direct link to the paper) The Lancet, 2003.

Christian M. Beausejour, Ana Krtolica, Francesco Galimi, Masashi Narita,
Scott W. Lowe, Paul Yaswen, and Judith Campisi (2003),
Reversal of human cellular senescence: roles of the p53 and p16 pathways,
The EMBO Journal, Vol.22. No.16 pp 4212-4222, 2003.

Tony Chih Yuan Chuang, Sharareh Moshir, Yuval Garini, Alice Ya-Chun Chuang, Ian T Young,
Bart Vermolen, Richard van den Doe, Virginie Mougey, Mathilde Perrin, Martina Braun, Paul Donald Kerr,
Thierry Fest, Petra Boukamp and Sabine Mai1 (2004),
The three-dimensional organization of telomeres in the nucleus of mammalian cells,
BMC Biology June 2004.

Santos, J.H., Meyer, J.N., Skorvaga, M., Annab, L.A., and Van Houten, B. (2004),
Mitochondrial hTERT exacerbases free-radical mediated mtDNA damage,
Aging Cell 3, 399-411. [Links/Mitochondrial hTERT, Images, Papers, Patents, Books].

Ralf Janknecht, edited by Varda Rotter (2004),
On the road to immortality: hTERT upregulation in cancer cells,
FEBS Letters, 564, 1-2, 23 April 2004, pp.9-13.

JW Shay and WE Wright (2005),
Senescence and Immortalization: the role telomeres and telomerase,
Carcinogenesis, Volume 26, Number 5 Pp. 867-874.

Jerry W. Shay and Woodring E. Wright (2005),
Use of Telomerase to Create Bioengineered Tissues,
New York Academy of Sciences, 2005.

Maria A Blasco (2005),
Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging,
The EMBO Journal, (2005) 24, 1095 1103.

Judith Campisi (2005),
Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbor,
Cell Vol 120, Issue 4, 25 February 2005, Pages 513-522

Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostack (2006), (Nobel Prize in Medicine, 2009),
Telomeres and Telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging, Nature Medicine, vol. 12, no. 10, October 2006.

Maurelli, Zambruno, et al. (2006), Inactivation of p16INK4a (inhibitor of cyclin-dependent kinase 4A) Immortalizes Primary Human Keratinocytes By Maintaining Cells in the Stem Cell Compartment,
The FASEB Journal, 2006;20:1516-1518.

Mogfield JE, Liu WR, Reid R (2006),
Adenoviral human telomerase reverse transcriptase dramatically improves ischemic wound healing without detrimental immune response in aged rabbit model,
Human Gene Therapy, 2006; 17(6): 651-660. This shows how telomerase may be activated via gene therapy using a viral vector.

Judy M.Y. Wong, and Kathleen Collins (2006),
Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis congenita,
Genes and Development 20:2848-2858, 2006.

Shay, J.W. and Wright, W.E. (2006),
Telomerase therapeutics for cancer: challenges and new directions,
Nature Reviews Drug Discovery 5, 577-584.

Chun-Hong Zhu, Vincent Mouly, Racquel N. Cooper, Kamel Mamchaoui, Anne Bigot, Jerry W. Shay, James P. Di Santo, Gillian S. Butler-Browne and Woodring E. Wright (2007),
Cellular senescence in human myoblasts is overcome by human telomerase reverse transcriptase and cyclin-dependent kinase 4: consequences in aging muscle and therapeutic strategies for muscular dystrophies.,
Aging Cell 6(4): 515-523.

Christine Kim Garcia, Woodring E. Wright and Jerry W. Shay (2007),
Human diseases of telomerase dysfunction: insights into tissue aging,
Nucleic Acids Research, 2007, Vol. 35, No. 22 7406-7416.

Ramiro E. Verdun and Jan Karlsreder (2007),
Replication and protection of telomeres,
Nature Vol.447, 21 June 2007.

Qin Ouyang, Gabriela Baerlocher, Irma Vulto and Peter M. Lansdorp (2007),
Telomere Length in Human Natural Killer Cell Subsets,
Hematopoietic Stem Cells VI, Volume 1106 published June 2007, Ann. N.Y. Acad. Sci., 1106: 240 252 (2007).

Laure Crabbe, Anna Jauch, Colleen M. Naeger, Heidi Holtgreve-Grez, and Jan Karlseder (2007),
Telomere dysfunction as a cause of genomic instability in Werner syndrome,
PNAS, February 13, 2007, vol. 104, no. 7, 2205-2210.

H. Jiang, Z. Ju, and K. L. Rudolph (2007),
Telomere Shortening and Aging,
Zeitshrift fur Gerontol and Geriatrics, 40:314-324 (2007).

Wilson, James M, (2008),
Adverse Events in Gene Transfer Trials and an Agenda for the New Year,
Human Gene Therapy, Volume 19, #1, January, 2008.

Geraldine Aubert and Peter M. Lansdorp, (2008),
Telomeres and Aging,
Physiological Review 88: 557-579, 2008. Includes 248 footnotes.

Flores, I. et al. (2008),
The longest telomeres: a general signature of adult stem cell compartments,
Genes and Development 22, 654-667.

Cong, Y. and Shay, J.W. (2008),
Actions of human telomerase beyond telomeres,
Cell Research 18, 725-732.

Paul L, Cattaneo M, D'Angelo A, Sampietro F, Fermo I, Razzari C, Fontana G, Eugene N, Jacques PF, Selhub J. (2009),
Telomere length in peripheral blood mononuclear cells is associated with folate status in men,
J Nutr. 2009 Jul;139(7):1273-8.

Tobias Else, (2009),
Telomeres and telomerase in adrenocortical tissue maintenance, carcinogenesis, and aging,
Journal of Molecular Endocrinology, (2009) 43, 131-141.

David R. Corey (2009),
Telomeres and Telomerase: From Discovery to Clinical Trials,
Chemistry & Biology, 16, Dec. 24, 2009.

Carroll, K.A., and Ly, H. (2009),
Telomere dysfunction in human diseases: the long and short of it!,
J. Clin. Exp. Pathol. 2, 528-543.

Rochette, P.J. and Brash, D.E. (2010),
Human Telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair,
PLos Genet. 6, e1000926 (2010).

Murnane, J.P., (2010),
Telomere loss as a mechanism for chromosome instability in human cancer,
Cancer Research 70, 4244-4259.

Ral, R. et. al. (2010),
The function of classical and alternative non-homologous end-joining pathways in the fusion of dysfunctional telomeres,
EMBO Journal 29, 2598-2610.

Paula Martinez and Maria A. Blasco (2011),
Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins,
Nature Reviews Cancer, vol. 11, March 2011, 161-176.

Are Telomeres the Key to Aging and Cancer? from the University of Utah's Genetic Science Learning Center, with charts, photos, and illustrations of telomere-related diseases.

Collected Papers of Elizabeth Blackburn: [Papers, Patents, Wikipedia, Links].
Collected Papers of Carol W Greider [Papers, Patents, Wikipedia, Links].
Collected Papers of Titia de Lange: [de Lange Lab, de Lange Lab/Publications; Papers, Patents, Wikipedia, Links, Books].
Collected Papers of C.B.Harley: [Papers, Patents, Links, Abstracts].
Collected Papers of Eric Kool: [Papers, Patents, Links].
Collected Papers of Jerry W. Shay: [Papers, Patents, Links, Shay/Wright Laboratory, Resume w/Papers].
Collected Papers of Woodring E. Wright: [Papers, Patents, Links, Resume w/Papers].
T.R. Cech, telomerase-related patents. [Patents, Papers, Links, Books].

_____7.1 Aging Damage to Telomeres
_______[Telomere Biology, Replicative Senescence, LEF, Links, Images, Papers, Patents, Books, Amazon, Wikipedia/Telomere].
See also TA Sciences Science Library.

Judy M. Y. Wong, Kathleen Collins (2003),
Telomere Maintenance and Disease,
The Lancet, May 13, 2003.

Bennet DC, Medrano EE, (2002),
Molecular Regulation of Melanocyte Senescence,
Pigment Cell Research, 2002.

_____7.2 Small Molecule Telomerase Activators and related molecules ((7)/Telomerase Activators, Index, List, lifexrefs3.html)
____________ [Index/Bioavailability, LEF, Links, Images, Papers, Patents, Books, Amazon;
_____________LEF, Links/Activate Telomerase, Images, Papers, Patents, Books, Amazon].

Cerni, C, (2000),
Telomeres, telomerase, and Myc,
Mutat. Res., Volume 462, Issue 1, January 2000, Pages 31-47.

Michael A. White, (2000),
METHODS AND COMPOSITIONS FOR INHIBITING OR STIMULATING TELOMERASE ASSEMBLY,
____Phosphoprotein 23 or p23, heat shock proteins 40, 70, and 90, and HOP (also called p60) improve telomerase assembly.

Helene LaBranche, Sophie Dupuis, Yaacov Ben-David, Maria-Rosa Bani, Raymund J. Wellinger, Benoit Chabot (1998),
Telomere enlongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase,
Nature Genetics vol 19, June 1998.
The derivative was an exogenously applied amino acid fragment of hnRNP A1 named UP1 = UAGGGU.
UAGGGU (UP1) RNA can be applied exogenously to cell lysates to produce telomere elongation.
It corresponds to the DNA hex repeat TAGGGT, which can enlongate a chain of TTAGGG repeats when inserted
between the first two TTs of TTAGGG. TTAGGG -> T(TAGGGT)TAGGG = TTAGGGTTAGGG.
"UP1 promotes telomere enlongation in mammalian cells." Experiments are described
featuring myc-tagged UP1 inserted with a virus. UP1 recombinant retroviruses were used.

Kavita Y. Sarin, Peggie Cheung, Daniel Gilison, Eunice Lee, Ruth I. Tennen, Estee Wang,
Maja K. Artandi, Anthony E. Oro, and Steven E. Artandi (2005),
Conditional telomerase induction causes proliferation of hair follicle stem cells,
Nature, 2005 August 18; 436(7053): 1048-1052.
See also iGrowHair Telomerase, which purports to communicate telomerase to the scalp using an acidophilus bacterium.

Christopher M. Counter and Blaine N. Armbruster (2007),
Telomere Elongation,
United States Patent 20070020722, filed in 2004, published 2007.
Identifies a hPot1-hTERT fusion protein deliverable in liposomes and otherwise to rapidly enlongate telomeres.

____________7.2.1 Geron Telomerase Activators mostly based on Astragalus and Ginsenosides [81s/6b, (7), Refs3]
______________(3b2/List, US Patent 7,846,904 B2, WO/2010/135247).
_____________[LEF, Links/Geron Telomerase Activators, lifexrefs3.html, Images, Papers, Patents, Books, Amazon;
_____________Index/Astragalus, Index/Astragalus Extract, 3b2, LEF, Links/Astragalus Extract, Images, Papers, Patents, Books, Amazon;
_____________Index/Ginseng, 3b2, LEF, Links/Ginsenosides, Images, Papers, Patents, Books, Amazon;
_____________Geron A, A', A'', B | TA Sciences | Sierra Sciences | Maximum Telomere Support | RevGenetics | Terraternal].

Michael D. West, Jerry Shay, Woodring E. Wright (1997),
Methods and Reagents for Lengthening Telomeres,
United States Patent 5686306, November 11, 1997, assigned to the Board of Regents, The University of Texas System. Prescribes making available to the cell oligonucleotides as nucleic acids typically including at least 2 to 3 telomeric repeat sequences, which in humans is 5'-TTAGGG-3' (SEQ. ID. NO:2).

Michael D. West, Jerry Shay, Woodring E. Wright (1998),
Method for screening for agents which increase telomerase activity in a cell, United States Patent 5830644, assigned to Geron Corporation, November 3, 1998. Contains many valuable references.

Hashimoto K., et.al, (2001 & 2003),
Skin tissue regeneration promoters comprising ginsenoside Rb1,
United States Patent 20030104079.

Jean-Louis Mergny, Jean-François Riou, Patrick Mailliet, Marie-Paule Teulade-Fichou and Eric Gilson (2002),
Natural and pharmacological regulation of telomerase,
Nucleic Acids Research, 2002, Vol. 30, No. 4 839-865.
Lei Hong, Wang Ben, et al. (2003),
Anti-Aging Effects of Astragalosides and its Mechanism of Action,
Acta Pharmacol Sin March 2003 24 (3), 230-234.
____Mice: "The results of many studies showed that AST was ineffective at 10, 20, 30 mg/kg, while it was effective at 40, 80, and 90 mg/kg."
____Long-telomere mice can tolerate large astragalus extract doses until antioxidant effects of astragalus inhibit aging.

Lei H, Wang B, Li WP, Yang Y, Zhou AW, Chen MZ (2003),
Anti-aging effect of astragalosides and its mechanism of action.,
Acta Pharmacol Sin. 2003 Mar;24(3):230-4.

Calvin B. Harley, et al. (2005),
Compositions and Methods for Increasing Telomerase Activity,
(Geron patent ap.) [Papers, Links].
___See also A' alternate version: Compositions and Methods for Increasing Telomerase Activity, or A''.
See also US Patent 7,846,904 B2, Dec.7,2010..

Calvin B. Harley, Hong Kong U. Patent, (2005),
Formulations Containing Astragalus Extracts and the Uses Thereof, European Patent Office.

Calvin, B. Harley, et. al, for Geron Corporation, (2005),
Compositions and Methods for Skin Conditioning
including small molecule telomerase activators such as astragaloside IV, cycloastragenol, astragenol, and astragaloside IV 16-one in glycerin, ect.

Calvin B Harley (2005),
Telomerase Therapeutics for Degenerative Diseases,
Current Molecular Medicine, Volume 5, Number 2, March 2005 , pp. 205-211(7).

Steven Russell Fauce, Beth D. Jamieson, Allison C. Chin, Ronald T. Mitsuyasu, Stan T. Parish, Hwee L. Ng, Christina M. Ramirez Kitchen, Otto O. Yang, Calvin B. Harley and Rita B. Effros (2008),
Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes,
The Journal of Immunology, 2008, 181: 7400-7406. Test of telomerase activator TAT2 (cycloastragenol). "Enhanced antiviral effects were abrogated in the presence of a potent and specific telomerase inhibitor, suggesting that TAT2 acts primarily through telomerase activation." See also the associated Geron News Release.

Min Yanga, Xin-Hua Qian, Dan-Hua Zhaoa and Su-Zhen Fu (2009). Effects of Astragalus polysaccharide on the erythroid lineage and microarray analysis in K562 cells, Journal of Ethnopharmacology, Nov 2009.

Geron (2010) intellectual property WO/2010/135247 (direct) for Enhanced-bioavailability telomerase activators.

________7.2.2 Bioavailablility of Astragalosides and Small-Molecule Telomerase Activators
_____________[Index/Bioavailability, LEF, Links/Bioavailability, Images, Papers, Patents, Books, Amazon;
_____________Links/Bioavailability of Astragalosides, Images, Papers, Patents, Books, Amazon; Chitosan, Sodium Deoxycholate].

Takakura, et al. (2001),
Telomerase activation by histone deacetylase inhibitor in normal cells,
Nucleic Acids Research, 2001, Vol. 29, No. 14 3006-3011

Jean-Louis Mergny, et al., (2002),
Natural and Pharmacological Regulation of Telomerase,
Nucleic Acids Research, 2002, volume 30, number 4, 839-864.

Maria Jose Cano-Cebrian, et al., (2005),
Intestinal Absorption Enhancement via the Paracellular Route by Fatty Acids, Chitosans, and Others: A Target for Drug Delivery,
Current Drug Delivery, 2005, 2, 9-22. Chitosan increases the bioavailability of astragaloside IV.

Huang CR, Wang GJ, Wu XL, Li H, Xie HT, Lv H, Sun JG, (2006),
Absorption enhancement study of astragaloside IV based on its transport mechanism in caco-2 cells,
Eur J Drug Metab Pharmacokinet. 2006 Jan-Mar;31(1):5-10.

Huang CR, Wang GJ, Wu XL, Li H, Xie HT, Lv H, Sun JG, (2006),
Absorption enhancement study of astragaloside IV based on its transport mechanism in caco-2 cells,
Eur J Drug Metab Pharmacokinet, 2006, Jan-Mar;31(1):5-10.
The bioavailability of astragaloside IV [Article, Papers], can be increased by chitosan [Wiki/chitosan, Links/chitosan] or sodium deoxycholate [Links/sodium deoxycholate, Books].

Calvin B Harley, Xu-Rong Jiang, Choy-Pik Chiu (2006),
Enhancing cell migration by increasing telomerase activity,
United States Patent 20060239974.

Arlona Tarkanyi, PhD thesis,
Pharmacological Regulation of Telomerase:..., phd.okm.gov.hu.

Won, J., Kim, M., Kim, N., Ahn, J.H., Lee, W.G., Kim, S.S., Chang,K.-Y., Yi, Y.-W., and Kim, T.K. (2006),
Small molecule-based reversible reprogramming of cellular lifespan,
Nat. Chem. Bio. 2:369-74, 2006.

Geron (2010) intellectual property WO/2010/135247 (direct) for Enhanced-bioavailability telomerase activators.

______7.2.3 DNA Nanocircles and Telomere Elongation: Eric T. Kool's Work. [Amazon].
_____________[LEF, Links/DNA Nanocircles for Telomere Enlongation, Images, Papers, Patents, Books, Amazon;
_____________Links/Eric T Kool Telomere Enlongation, Images, Papers, Patents, Books, Amazon].

Ulf M. Lindstrom, Ravi A. Chandrasekaran, Lucian Orbai, Sandra A. Helquist, Gregory P. Miller, Emin Oroudjev, Helen G. Hansma, and Eric T. Kool (2002),
Artificial human telomeres from DNA nanocircle templates,
PNAS, December 10, 2002, vol. 99, no. 25, 15953-15958.

Dr. Eric T. Kool, (2003),
(WO/2003/057849) TELOMERE-ENCODING SYNTHETIC DNA NANOCIRCLES, AND THEIR USE FOR THE ELONGATION OF TELOMERE REPEATS,
World Intellectual Property Organization.

Jorg S. Hartig and Eric T. Kool (2004),
Small circular DNAs for synthesis of the human telomere repeat: varied sizes, structures and telomere-encoding activities,
Nucleic Acids Research 2004 vol.32(no.19): pg.152.

______Temporary Catch-All

Alan K. Meeker, Jessica L. Hicks, Christine A. Iacobuzio-Donahue, Elizabeth A. Montgomery, William H. Westra, Theresa Y. Chan, Brigitte M. Ronnett and Angelo M. De Marzo, (2004),
Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis,
Clinical Cancer Research Vol. 10, 3317-3326, May 15, 2004.

Bekaert s, Koll S, et al. (2002),
Comparing telomere lengths of sister chromatids in human lymphocytes using 3-dimensional confocal microscopy,
Cytometry, 2002.

Yong-Ouk You, Gene Lee and Byung-Moo Min, (2000),
Retinoic Acid Extends the in Vitro Life Span of Normal Human Oral Keratinocytes by Decreasing p16INK4A Expression and Maintaining Telomerase Activity,
Biochemical and Biophysical Research Communications, Volume 268, Issue 2, 16 February 2000, Pages 268-274.

Maurelli, Zambruno, et al. (2006), Inactivation of p16INK4a (inhibitor of cyclin-dependent kinase 4A) Immortalizes Primary Human Keratinocytes By Maintaining Cells in the Stem Cell Compartment,
The FASEB Journal, 2006;20:1516-1518.

Kayo Furumotoa, Eiji Inouea, Norio Nagaoa, Eiso Hiyamab and Nobuhiko Miwa (1998),
Age-dependent telomere shortening is slowed down by enrichment of intracellular vitamin C via suppression of oxidative stress,
Life Sciences, Volume 63, Issue 11, 7 August 1998, Pages 935-948.

HANNON, Gregory, Jing J. WANG, BEACH, David, H. (1999),
(WO/1999/035243) EXTENSION OF CELLULAR LIFESPAN, METHODS AND REAGENTS,
[Links].

Hideki Mizuno, Shilagardi Khurts, Takahiko Seki, Yasuhide Hirota, Shuichi Kaneko and Seishi Murakami (2007),
Human Telomerase Exists in Two Distinct Active Complexes In Vivo (one is complexed with HSP 90),
Journal of Biochemistry, 2007 141(5):641-652.

Richard C. Allsopp, Samuel Cheshier and Irving L. Weissman (2002),
Telomerase Activation and Rejuvenation of Telomere Length in Stimulated T Cells Derived from Serially Transplanted Hematopoietic Stem Cells,
JEM, 2 December 2002. Antigenic stimulation activates telomerase in T-cells.

_____7.2.4 Sierra Sciences: the hTERT Promoter and Methods and Compositions for modulating hTERT expression [Sierra Sciences].
_____________[LEF/William Andrews, Sierra Sciences, Links/Sierra Sciences, Images, Papers, Patents, Books;
_____________Links/the hTERT promoter, Images, Papers, Patents, Books, Amazon;
_____________LEF/modulating hTERT expression, Links, Images, Papers, Patents, Books, Amazon]. (WO/2002/101010)
______________METHODS AND COMPOSITIONS FOR MODULATING
______________TELOMERASE REVERSE TRANSCRIPTASE (TERT) EXPRESSION].

William H. Andrews, C.A.Foster, S. Fraser, Hamid Mohammedpour, of Sierra Sciences (2004):
Methods and Compositions for Modulating Telomerase Reverse Transcriptase (TERT) Expression,
United States Patent No. 6,686,159 B2, Andrews, et al., Feb 3, 2004. Explains the hTERT repressor in the hTERT promotor and means of interfering with hTERT repression.

William H. Andrews, Laura Briggs, Lancer K. Brown, Christopher A. Foster, Mieczyslaw A. Piatyszek, Assignee: Sierra Sciences, Inc. (2005),
Assays for TERT promoter modulatory agents..., US Patent # 7226744.

Andrews; William H., Foster; Christopher A., Fraser; Stephanie, Mohammadpour; Hamid, Briggs; Laura, Assignee: Sierra Sciences, Inc. (2004),
Methods and compositions for modulating telomerase reverse transcriptase (TERT) expression.,
Appl. No.: 10/826,466.

Yi-hsin HSU, Jing-jer LIN (2005),
Telomere and telomerase as targets for anti-cancer and regeneration therapies,
Acta Pharmacologica Sinica, 2005 May; 26 (5): 513-518.

___________7.2.5 Nitric Oxide as a Telomerase Activator
______________[Index/Nitric Oxide, LEF/Nitric Oxide, NO More Heart Disease,
______________Links/Nitric Oxide activates telomerase, Images, Papers, Patents, Books].
______________[LEF, Links/Nitric Oxide as a Telomerase Activator, Images, Papers, Patents, Books].

M. Vasa, K Breitschopf, AM Zeiher, S Dimmeler (2000),
Nitric Oxide Activates Telomerase and Delays Endothelial Cell Senescence,
Circulation Research, 2000, 87: pp. 450-452. - Am Heart Assoc.
____PDF sup_notes: Nitric Oxide Activates Telomerase and Delays Endothelial Cell Senescence, Univ. of Frankfort.

Toshio Hayashi, Hisako Matsui-Hirai, Asaka Miyazaki-Akita, Akiko Fukatsu, Jun Funami,
Qun-Fang Ding, Sumitra Kamalanathan, Yuichi Hattori, Louis J. Ignarro, and Akihisa Iguchi (2006),
Endothelial cellular senescence is inhibited by nitric oxide: Implications in atherosclerosis associated with menopause and diabetes,
PNAS, November 7, 2006, vol. 103, no. 45, pp. 17018-17023.

Erusalimsky JD, (2009),
Vascular endothelial senescence: from mechanisms to pathophysiology,
Journal of Applied Physiology, 106/1/326, 2009.

Hong Y, Quintero M, Frakich NM, Trivier E, Erusalimsky JD (2007),
Evidence against the involvement of nitric oxide in the modulation of telomerase activity or replicative capacity of human endothelial cells,
Experimental Gerontology 42: 904-910, 2007.

Judith Haendeler (2006),
Nitric oxide and endothelial cell aging,
European Journal of Clinical Pharmacology, Volume 62, Supplement 1 / February, 2006.

Farsetti A, Grasselli A, Bacchetti S, Gaetano C, Capogrossi MC (2009),
The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling,
Journal of Applied Physiology 106: 333-337, 2009.

___________7.2.6 Novel Wistar Institute Small-Molecule Telomerase Activators
____________[Tri-Phenyl Compounds, Links/Wistar Institute Telomerase Activators, Images, Papers, Patents, Books].

See Aviv Gazit et al (2008), TELOMERASE ACTIVATING COMPOUNDS AND METHODS OF USE THEREOF,
US Patent, US Patent App. 12/602,956, 2008, WO Patent WO/2008/149,353, 2008. (See PDF version.)
Tri-Phenyl Compound Telomerase Activators developed at Ben Gurion University on the Negev [Links, Images, Papers, Books].

Novel Telomerase Activators, Ben Gurion University on the Negev. BGN Technologies.

Andrew J. Gillis, Anthony, P. Schuller & Emmanuel Skordalakes (2008),
Structure of the Tribolium castaneum telomerase catalytic subunit TERT,
Nature, 455:633-637, 2008.
Referenced in The Wistar Institute/Design of Novel Molecules That Regulate Telomerase.

Rouda S, Skordales E. Structure, (2007), Nov. 15(11):1403-12,
Structure of the RNA binding domain of telomerase: Implications for RNA recognition and binding, Referenced in The Wistar Institute/Design of Novel Molecules That Regulate Telomerase.
____See Decipering Of Telomerase Structure Opens Door To New Cancer, Aging Treatments at Medical News Today describes work by Emmanuel Skordalakes on telomerase structure.

___________7.2.7 Androgens as Small-Molecule Telomerase Activators
___________[List/Androgens, Links, Images, Papers, Patents; Books/Androgens and Aging; LEF/Androgens, Wikipedia].

Rodrigo T. Calado, William T. Yewdell, Keisha L. Wilkerson, Joshua A. Regal,
Sachiko Kajigaya, Constantine A. Stratakis, and Neal S. Young (2009),
Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells,
Blood, 10 September 2009, Vol. 114, No. 11, pp. 2236-2243.

Chuanhai Guo, Blaine N. Armbruster, David T. Price, Christpher M. Counter, (2003),
In Vivo Regulation of hTERT Expression and Telomerase Activity by Androgen,
Journal of the American Academy of Dermatology, Volume 170, Issue 2, Part 1, Pages 615-618 (August 2003).
____Other investigators speculate that androgens are converted to estrogens before interacting with the hTERT promoter to activate telomerase.

_____7.3 Telomerase Inhibitors [SupNotes3b/telomerase inhibitors, List, LEF, Links/Telomerase Inhibitors, Images, Papers, Patents, Books].

Mayank Singh and Neeta Singh, (2009),
Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells,
Molecular and Cellular Biochemistry, Volume 325, Numbers 1-2 / May, 2009, Pages 107-119.
Theeffectiveness of curcumin for this application derives from its properties as a telomerase inhibitor.

Park SE, Park C, Kim SH, Hossain MA, Kim MY, Chung HY, Son WS, Kim GY, Choi YH, Kim ND (2009),
Korean red ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells.,
Journal of Ethnopharmacology, 2009 Jan 21;121(2):304-12.

Moriai M, Tsuji N, Kobayashi D, Kuribayashi K, Watanabe N, (2009),
Down-regulation of hTERT expression plays an important role in 15-deoxy-Delta12,14-prostaglandin J2-induced apoptosis in cancer cells,
1: International Journal of Oncology, 2009 May; 34(5): 1363-1372.

____7.4 The hTERT Promoter [Index, Links/hTERT Promoter, Images, Papers, Patents, Books].

Horikawa I., Cable P. L., Afshari C., Barrett J. C. (1999),
Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene,
Cancer Research, 59: 826-830, 1999.

William H. Andrews, C.A.Foster, S. Fraser, Hamid Mohammedpour, of Sierra Sciences (2004):
Methods and Compositions for Modulating Telomerase Reverse Transcriptase (TERT) Expression,
United States Patent No. 6,686,159 B2, Andrews, et al., Feb 3, 2004.
Explains the hTERT repressor in the hTERT promotor and means of interfering with hTERT repression.

William H. Andrews, Laura Briggs, Lancer K. Brown, Christopher A. Foster, Mieczyslaw A. Piatyszek, Assignee: Sierra Sciences, Inc. (2005),
Assays for TERT promoter modulatory agents..., Telomerase promoter driving expression of therapeutic gene sequences.

M Wick, D Zubov, G Hagen (1999),
Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT),
Gene, Volume 232, Issue 1, 17 May 1999, Pages 97-106.

Cong, YS (1999),
The Human Telomerase Catalytic Subunit hTERT: organization of the gene and characterization of the promoter,
Human Molecular Genetics, 1999, vol.8, no.1, 137-142.

Yu-Sheng Cong, Woodring E. Wright, and Jerry W. Shay, Human Telomerase and Its Regulation.

Izumi Horikawa, P. LouAnn Cable, Cynthia Afshari and J. Carl Barrett, (1999),
Cloning and Characterization of the Promoter Region of Human Telomerase Reverse Transcriptase Gene ,
Cancer Research, 59, 826-830, February 1, 1999.
[Papers, Books].

Takakura, M., Kanaya,T., et al (1999),
Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells,
Cancer Research, 59, 551-557.

M.P. Mattson (2001),
Telomerase, Aging and Disease (Advances in Cell Aging and Gerontology),
Elsevier, 2001.

Wu, (1999),
c-Myc activates hTERT promoter, Nature Genetics, 1999.
[Links, Papers, Books].

Theodora R. Devereux, Izumi Horikawa, Colleen H. Anna, Lois A. Annab, Cynthia A. Afshari and J. Carl Barrett, (1999),
DNA Methylation Analysis of the Promoter Region of the Human Telomerase Reverse Transcriptase (hTERT) Gene,
Cancer Research 59, 6087-6090, December 1, 1999.

Joseph C. Poole, Lucy G. Andrews and Trygve O. Tollefsbol (2001),
Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT),
Gene, Volume 269, Issues 1-2, 16 May 2001, Pages 1-12.

Sang Sun Kang, Taegun Kwon, Do Yoon Kwon, and Su Il Do, (1999),
Akt Protein Kinase Enhances Human Telomerase Activity through Phosphorylation of Telomerase Reverse Transcriptase Subunit,
Journal of Biological Chemistry, Vol. 274, Issue 19, 13085-13090, May 7, 1999.

_____7.5 Telomere Epigenetics [Links/Epigenetics; Links/Telomere Epigenetics, Images, Papers, Patents, Books; Books/Epigenetic Control;
_______Index/Telomeric Chromatin].

Theodora R. Devereux, Izumi Horikawa, Colleen H. Anna, Lois A. Annab, Cynthia A. Afshari and J. Carl Barrett (1999),
DNA Methylation Analysis of the Promoter Region of the Human Telomerase Reverse Transcriptase (hTERT) Gene,
Cancer Research 59, 6087-6090, December 1, 1999.
This paper includes an analysis of the hTERT promoter.
"Most of the hTERT-negative normal cells and about one-third of the hTERT-expressing cell lines
had the unmethylated/hypomethylated promoter, whereas the other hTERT-expressing cell lines
showed partial or total methylation of the promoter. The promoter of one hTERT-negative
fibroblast cell line, SUSM-1, was methylated at all sites examined."

Farwell, Shera, et al. (2000),
Genetic and Epigenetic Changes in Human Epithelial Cells Immortalized by Telomerase,
American Journal of Pathology 2000 May; 156(5): 1537 1547.
___It may be necessary to down-regulate p16INK4a and p14ARF in breast cell or foreskin tissue for these to become immortal.

Kiyoaki Nomoto1, Masato Maekawa1, Kokichi Sugano1, Mineko Ushiama1,
Noriko Fukayama1, Shin Fujita2 and Tadao Kakizoe3 (2002),
Methylation Status and Expression of Human Telomerase Reverse Transcriptase mRNA in Relation to Hypermethylation of the p16 gene in Colorectal Cancers as Analyzed by Bisulfite PCR-SSCP,
Jpn. J. Clin. Oncol. (2002) 32 (1): 3-8.

Isabelle Guilleret, Pu Yan (2002),
Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity,
International Journal of Cancer, Volume 101, Issue 4 , Pages 335 - 341, 7 Aug 2002.

Widschwendter A, Müller HM, Hubalek MM, Wiedemair A, Fiegl H, Goebel G,
Mueller-Holzner E, Marth C, Widschwendter M. (2004),
Methylation status and expression of human telomerase reverse transcriptase in ovarian and cervical cancer,
Gynecol Oncol. 2004 May;93(2):407-16.
"No correlation was detected between hypermethylation of hTERT and hTERT mRNA expression.".

Maria A. Blasco (2004),
Telomere epigenetics: a higher-order control of telomere length in mammalian cells,
Carcinogenesis, Vol. 25, No. 7, 1083-1087, July 2004.
___ hRAP1 is recruited by TRF2 to human telomeres. hRAP1 is the homologue of yeast RAP1 protein and its over-expression causes telomere elongation.

Garcia-Cao, M., O'Sullivan, R., Peters, A.H., Jenuwein, T., and Blasco, M.A. (2004),
Epigenetic regulation of telomere length in mammalian cells by SUV39h1 and SUV39h2 histone methyltransferases,
Nature Genetics 36, 94-99.

Gonzalo, S., et al. (2005),
The role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin,
Nature Cell Biology 7, 420-428.

Gonzalo, S. et al. (2006),
DNA methylases control telomere length and telomere recombination in mammalian cells,
Nature Cell Biology 8, 416-424.

Rebekah L. Zinn, Kevin Pruitt, Sayaka Eguchi, Stephen B. Baylin, and James G. Herman, (2007),
hTERT is Expressed in Cancer Cell Lines Despite Promoter DNA Methylation by Preservation of Unmethylated DNA and Active Chromatin around the Transcription Start Site,
Cancer Research 2007 67; (1) January 1, 2007, pp.194-201.

Azzalin, C.M., Reichenbach, P. Khorlauli, L., Glulotto, E., and Lingner, J. (2007),
Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends, Science 318, 789-801.

Benetti, R. et al. (2007),
SUV4-20h deficiency results in telomere enlongation and derepression of telomere recombination,
Journal of Cell Biology 178, 925-936.

Benetti, R., Garcia-Cao,M. and Blasco, M.A. (2007),
Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres,
Nature Genetics 39, 243-250.

Shoeftner, S., and Blasco, M.A. (2008),
Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II,
Nature Cell Biol. 10, 228-236.

Benetti, R., et al. (2008),
A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rb12-dependent regulation of DNA methyltransferases,
Nature Struct. Mol. Biol 15, 268-279.

See Schoeftner, S. and Blasco, M.A. (2009),
A 'higher order' of telomere regulation: telomere heterochromatin and telomeric RNAs,
EMBO Journal 28, 2323-2336.

Marion, R.M., et al. (2009),
Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells,
Cell Stem Cell 4, 141-154.
Describes epigenetic markers of Embyronic Stem cells during nuclear reprogramming.

Paula Martinez and Maria A. Blasco (2011),
Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins,
Nature Reveiws Cancer, vol. 11, March 2011, 161-176.

_____7.6 The Telomere Position Effect and Youthful Patterns of Gene Expression
_______[Links/The Telomere Position Effect, Images, Video, Papers, Books].

DE Gottschling, OM Aparicio, BL Billington, VA, et al. (1990),
Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription,
Cell, Vol 63, 751-762, 16 November 1990.
Wright, W. E. and J.W.Shay (1992),
Telomere positional effects and the regulation of cellular senescence,
Trends Genet 8:193-197.

Joseph A. Baur, Ying Zou, Jerry W. Shay, Woodring E. Wright (2001),
Telomere Position Effect in Human Cells,
Science 15 June 2001: Vol. 292. no. 5524, pp. 2075 - 2077.

Carmia Borek (2002),
Telomere Control and Cellular Aging,
Life Extension Magazine, September 2002.

Joseph A. Baur, Woodring E. Wright, Jerry W. Shay (2004),
Analysis of Mammalian Telomere Position Effect,
Epigenetics Protocols, 2004.

______7.7 Telomere T-Loop and D-Loop
_________[Links/The Telomere t-loop, Images, Video, Papers, Books; Links/The Telomere d-loop, Images, Video, Papers, Books].

Carol W. Greider (1999),
Telomeres Do D-Loop T-Loop Minireview.

Jerry W. Shay (1999),
On telomeric t-loops and d-loops.

J.L. Munoz-Jordan, G.A. Cross, T. de Lange, and J. D. Griffith (2001),
T-loops at typanosome telomeres,
EMBO Journal 20, 579-588.

_____7.8 Telomere Capping Proteins
________[Index/Telomere Loop Control Proteins, Index/Mammalian Telomere Protein Factors with The Telomere Interactome,
________Links/Telomere Capping Proteins, Images, Video, Papers, Books; Amazon/Shelterin, Amazon/The Telosome].

Lustig, A.J., Kurtz, S., and Shore, D. (1990),
Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length,
Science 250, 549-553.

Fang G, Cech TR (1993),
The beta subunit of Oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA,
Cell 1993, 74:875-885. [Links/DNA G-quartet formation].

Henrik Tommerup, Athanasios Dousmanis, and Titia de Lange (1994),
Unusual Chromatin in Human Telomeres,
Molecular and Cellular Biology, Sept. 1994, p.5777-5785.

Chong, L., van Steensel, B., Broccoli, D., Erdjument-Bromage, H., Hannish, J., Tempst, T., and de Lange, T., (1995),
A human telomeric protein (TRF1),
Science 270, 1663-1667.

A. Krauskopf, Elizabeth H. Blackburn (1996),
Control of telomere growth by interactions of RAP1 with the most distal telomeric repeats,
Nature 383, 354-357. [Shelterin/RAP1].

Nugent, C. I., T. R. Hughes, N. F. Lue, and V. Lundblad (1996),
Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance,
Science 274:249-252. [Links/Cdc13p].

Broccoli D, Smogorzewska A, Chong L, de Lange T (1997),
Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2,
Nature Genetics 1997, 17:231-235. [Links/Myb-related proteins, Shelterin/TRF1, Shelterin/TRF2].

Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E (1997),
Telomeric localization of TRF2, a novel human telobox protein,
Nature Genetics 1997, 17:236-239. [Links/telobox proteins, Shelterin/TRF2].

Bianchi, A, Smith, S, Chong, L, Elias, P, and de Lange, T. (1997),
TRF1 is a dimer and bends telomeric DNA,
EMBO Journal, 16: 1785-1784. [Shelterin/TRF1].

Shen M, Haggblom C, Vogt M, Hunter T, Lu KP (1997):
Characterization and cell cycle regulation of the related human telomeric proteins Pin2 and TRF1 suggest a role in mitosis,
Proc Natl Acad Sci USA 1997, 94:13618-13623. [Shelterin/TRF1, Pin2].

van Steensel B, de Lange T (1997),
Control of telomere length by the human telomeric protein TRF1,
Nature 1997, 385:740-743. [Shelterin/TRF1].

Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR (1997),
Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines,
Nature Med 1997, 3:1271-1274.

Horvath MP, Schweiker VL, Bevilacqua JM, Ruggles JA, Schultz SC (1998),
Crystal structure of the Oxytricha nova telomere end binding protein complexed with single strand DNA,
Cell 1998, 95:963-974.

Smith S, Giriat I, Schmitt A, de Lange T (1998),
Tankyrase, a poly(ADP-ribose) polymerase at human telomeres,
Science 1998, 282:1484-1487. [List(Telomerase Activators)/Tankyrase].

van Steensel B, Smogorzewska A, de Lange T (1998),
TRF2 protects human telomeres from end-to-end fusions,
Cell 1998, 92:401-413. [Shelterin/TRF2].

d'Adda di Fagagna, F., Hande, M.P., Tong, W.-M., Lansdorp, P.M., Wang, Z.Q., Jackson, S.P. (1999),
Functions of poly(ADP-ribose) polymerase in controlling telomere length and chromosomal stability,
Nature Genetics 23, 76-80.

Karlsreder J., Broccoli, D., Dai, Y., Hardy, S., and de Lange, T. (1999),
P53 and ATM-dependent apoptosis induced by telomeres lacking TRF2,
Science 283, 1321-1325. [Shelterin/TRF2].

S. Le, J.K. Moore, J.E. Haber, and Carol W. Greider (1999),
RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase,
Genetics 152, 143-152. [Telomere Management Proteins/RAD51D, Telomere Interactome/RAD50].

S. H. Kim, P. Kaminker, and Judith Campisi (1999),
TIN2, a new regulator of telomere length in human cells,
Nature Genetics 23, 405-412. [Shelterin/TIN2].

K.G. Murti and D.M.Prescott (1999),
Telomeres of polytene chromosomes in a ciliated protozoan terminate in duplex DNA loops,
PNAS, December 7, 1999, Vol 96, No. 25, pp.14436-14439.

Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999),
Mammalian telomeres end in a large duplex loop,
Cell 1999, 97:503-514.

Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T (1999),
p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2,
Science 1999, 283:1321-1325. [Shelterin/TRF2, Telomere Interactome/ATM, p53].

Iftode C, Daniely Y, Borowiec JA (1999),
Replication protein A (RPA): the eukaryotic SSB,
Crit Rev Biochem Mol Biol 1999, 34:141-180.

Smith S, de Lange T (1999),
Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes,
Journal of Cell Science 1999, 112:3649-3656.

Huffman, K.E., Levene, S.D., Tesmer, V.M., Shay, J.W., Wright, W.E. (2000),
Telomere shortening is proportional to the size of the G-rich telomeric 3'-overhang,
Journal of Biological Chemistry, 275, 19719-19722.

Song K, Jung D, Jung Y, Lee S.G, Lee I (2000),
Interaction of human Ku70 with TRF2,
FEBS Letters 2000, 481:81-85. [Shelterin/TRF2, Ku70].

Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T (2000),
Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres,
Nature Genetics, 2000, 25:347-352. [Shelterin/TRF2, RAD50, MRE11, NBS1].

Smith S, de Lange T (2000),
Tankyrase promotes telomere elongation in human cells,
Curr Biol 2000, 10:1299-1302. [TA/Tankyrase].

Nai-Wen Chi and Harvey F. Lodish (2000),
Tankyrase Is a Golgi-associated Mitogen-activated Protein Kinase Substrate That Interacts with IRAP in GLUT4 Vesicles,
Journal of Biological Chemistry, December 8, 2000, 275, 38437-38444. This paper describes the phosphorylation of tankyrase 1 in insulin-stimulated cells. "Tankyrase is a novel signaling target of mitogen-activated protein kinase (MAPK); it is stoichiometrically phosphorylated upon insulin stimulation [Images, Papers, Patents, Books]. Phosphorylation enhances the poly(ADP-ribose) polymerase activity of tankyrase... (requiring a NAD+ (Nicotinamide adenine dinucleotide) substrate)... The phosphorylation of tankyrase by MAPK increases its PARP activity..." Chi and Lodish also found tankyrase 1 phosphorylation due to stimulation of tankyrase 1 with PDGF and EGF. "...Tankyrase is quantitatively phosphorylated on certain serine residues by MAPK upon stimulation with insulin, PDGF, and EGF." Phosphorylation allows tankyrase to transduce MAPK signaling into poly(ADP-ribosyl)ation of effector proteins.

H.L Hsu, , D. Gilley, S.A. Galande, M.P. Hande, B. Allen, S.H. Kim, S.H., G.C. Li, Judith Campisi, T. Kohwi-Shigematsu, and D.J. Chen, (2000).
Ku acts in a unique way at the mammalian telomere to prevent end joining,
Genes and Development, 14, 2807-2812.
The Ku proteins are often represented by 2011 as binding at spot where the 3' strand separates from duplex telomere DNA.

Li B, Oestreich S, de Lange T (2000),
Identification of human Rap1: implications for telomere evolution,
Cell 2000, 101:471-483.

Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G, de Lange T (2000),
Control of human telomere length by TRF1 and TRF2,
Mol Cell Biol 2000, 20:1659-1668.

Zhou BB, Elledge SJ (2000),
The DNA damage response: putting checkpoints in perspective,
. Nature 2000, 408:433-439.

Li, B, and Comai, L. (2000),
Functional interaction between KU and the werner syndrome protein in DNA end processing,
Journal of Biological Chemistry 275: 28349-28352.

Ghosh, I., Hamilton, A.D., and Regan, L. (2000),
Antiparallel Leucine Zipper-Directed Protein Reassembly: Application of Green Fluorescent Protein,
Chem Soc 122, 5658.

Blackburn, E. H. (2000),
Telomere states and cell fates,
Nature 408:53-56.

Chandra, A., T. R. Hughes, C. I. Nugent, and V. Lundblad (2001),
Cdc13 both positively and negatively regulates telomere replication,
Genes and Development, 15:404-414.

Kishi S, Zhou XZ, Ziv Y, Khoo C, Hill DE, Shiloh Y, Lu KP (2001),
Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks,
J Biol Chem 2001, 276:29282-29291.

S. E. Peterson, A.E. Stellwagen, S.J. Diede, M.S. Singer, Z.W. Haimberger, C.O. Johnson, M. Tzoneva, and D.E. Gottschling (2001),
The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku,
Nature Genetics 27, 64-67.

Baumann P, Cech TR (2001),
Pot1, the putative telomere end-binding protein in fission yeast and humans,
Science 2001, 292:1171-1175.

Fairall L, Chapman L, Moss H, de Lange T, Rhodes D (2001),
Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2,
Mol Cell 2001, 8:351-361.

Stansel RM, de Lange T, Griffith JD (2001),
T-loop assembly in vitro involves binding of TRF2 near the 3' telomeric overhang,
EMBO Jouranal 2001, 20:5532-5540.

Blackburn EH (2001),
Switching and signaling at the telomere,
Cell 2001, 106:661-673.

Wright WE, Shay JW (2001),
Cellular senescence as a tumor-protection mechanism: the essential role of counting,
Curr Opin Genet Dev 2001, 11:98-103.

Zhou XZ, Lu KP (2001),
The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor,
Cell 2001, 107:347-359.

Pennock, E., K. Buckley, and V. Lundblad (2001),
Cdc13 delivers separate complexes to the telomere for end protection and replication,
Cell 104:387-396.

Kaminker PG, Kim S-H, Taylor RD, Zebarjadian Y, Funk WD, Morin GB, Yaswen P, Campisi J (2001),
TANK2, a new TRF1-associated PARP, causes rapid induction of cell death upon overexpression,
J Biol Chem 276: 35891–35899. Check: TANK2 = Tankyrase 2.

Moshous, D., Callebaut, I., de Chasseval, R., Comeo, B. Cavez-zana-Calvo, M.,
Le Deist, F., Tezcan, I., Sanal, O., Bertrand, Y., Philippe, N., et al. (2001),
Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency,
Cell 105, 177-186.

Bailey, S.M., Comforth M.N., Kurimasa, A., Chen, D.J., and Goodwin, E.H. (2001),
Strand-specific postreplicative processing of mammalian telomeres,
Science, 293, 2462-2465.

de Lange, T. (2001),
Telomere capping - one strand fits all,
Science, 292, 1075-1076.

Espejel, S et al. (2002), Mammalian KU86 mediates chromosomal fusions and apoptosis caused by critically short telomeres,
EMBO Journal 21, 2207-2219.

Smogorzewska, A., Karlsreder, J., Holtgreve-Grez, H., Jauch, A., and de Lange, T. (2002),
DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2,
Current Biology 12: 1635-1644.

Ancelin, K., et al. (2002),
Targeting assay to study the cis functions of human telomeric proteins: evidence for the inibition of telomerase by TRF1 and and activation of telomere degradation by TRF2,
Mol. Cell. Biol. 22, 3474-3487.

Jörg F. Rippmann, Klaus Damma and Andreas Schnapp (2002),
Functional Characterization of the Poly(ADP-ribose) Polymerase Activity of Tankyrase 1, a Potential Regulator of Telomere Length,
Journal of Molecular Biology Volume 323, Issue 2, 18 October 2002, Pages 217-224.

Marsischky, G.T., Wilson, B.A. and Collier, R.J. (2003),
Role of glutamic acid of human poly-ADP-ribose polymerase in polymer formation. Evidence for active site similarities to the ADP-ribosylating toxins,
J. Biol. Chem. 270, 3247-3254.

Cook, B. D., J. N. Dynek, W. Chang, G. Shostak, and S. Smith (2002),
Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres,
Mol. Cell. Biol, 22:332-342. See Tankyrase 1.

Baumann, P., E. Podell, and T. R. Cech (2002),
Human Pot1 (protection of telomeres) protein: cytolocalization, gene structure, and alternative splicing, Mol. Cell. Biol. 22:8079-8087.

Granger, M.P., Wright W.E., and Shay, J.W. (2002),
Telomerase in cancer and aging,
Crit Rev Oncol Hematol 41, 29-40.

Paulmurugan, R., Umezawa, Y., and Gambhir, S.S. (2002),
Noninvasive imaging of protein-protein interactions in living subjects by using reporter protein complementation and reconstitution strategies,
Proc Natl Acad Sci USA 99, 15608-15613.

Stavropoulos, D.J., Bradshaw, P.S., Li, X., Pasic, I., Truong, K., Ikura, M., Ungrin, M., and Meyn, M.S. (2002),
The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis,
Human Molecular Genetics 11, 3135-3144.

Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA (2002),
Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases,
J Biol Chem 2002, 277:41110-41119.

Nakamura M, Zhou XZ, Kishi S, Lu KP (2002),
Involvement of the telomeric protein Pin2/TRF1 in the regulation of the mitotic spindle,
FEBS Letters 2002, 514:193-198.

Cong YS, Wright WE, Shay JW (2002),
Human telomerase and its regulation,
Microbiol Mol Biol Rev 2002, 66:407-425.

Maser RS, DePinho RA (2002),
Connecting chromosomes, crisis, and cancer,
Science 2002, 297:565-569.

Kim SH, Kaminker P, Campisi J (2002),
Telomeres, aging and cancer: in search of a happy ending,
Oncogene 2002, 21:503-511.

de Lange (2002), Protection of mammalian telomeres,
Oncogene, 21: 532-540.

Collins, K., and Mitchell, J.R. (2002),
Telomerase in the human organism,
Oncogene 21, 564-579.

Hu, C.D., Chinenov, Y., and Kerppola, T.K. (2002),
Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation,
Mol Cell 9, 789-798.

Iwano, T., Tachibana, M, Reth, M., and Shinkai, Y. (2003),
Importance of TRF1 for Functional Telomere Structure,
Journal of Biological Chemistry 279, 1442-1448 (2003).

d'Adda di Fagagna, F., P. M. Reaper, L. Clay-Farrace, H. Fiegler, P. Carr, T. Von Zglinicki, G. Saretzki, N. P. Carter, and S. P. Jackson (2003),
A DNA damage checkpoint response in telomere-initiated senescence,
Nature 426:194-198.

Takai, H., Smogorzewska, A., and de Lange T. (2003),
DNA damage foci at dysfunctional telomeres,
Current Biology 13, 1549-1556.

Hu, C.D., and Kerppola, T.K. (2003),
Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis,
Nature Biotechnology 21, 539-545.

Loayza D, de Lange T (2003),
POT1 as a terminal transducer of TRF1 telomere length control,
Nature 2003, 424:1013-1018.

Takai, H., Smogorzewska, A., de Lange, T. (2003),
DNA damage foci at dysfunctional telomeres,
Current Biology 13: 1549-1556.

Chang W, Dynek JN, Smith S (2003),
TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres,
Genes and Development 2003, 17:1328-1333.

Li B, de Lange T (2003),
Rap1 affects the length and heterogeneity of human telomeres,
Mol Biol Cell, 2003, 14:5060-5068.

Lei M, Podell ER, Baumann P, Cech TR (2003),
DNA self-recognition in the structure of Pot1 bound to telomeric single-stranded DNA,
Nature 2003, 426:198-203.

Zhu XD, Niedernhofer L, Kuster B, Mann M, Hoeijmakers JH, de Lange T (2003),
ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes,
Mol Cell 2003, 12:1489-1498.

Zou L, Elledge SJ (2003),
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes,
Science 2003, 300:1542-1548.

Deng Z, Atanasiu C, Burg JS, Broccoli D, Lieberman PM (2003),
Telomere repeat binding factors TRF1, TRF2, and hRAP1 modulate replication of Epstein-Barr virus OriP,
J Virol 2003, 77:11992-12001.

Karlseder, J., Kachatrian, L., Takai, H., Mercer, K., Hingorani, S., Jacks, T., and de Lange, T. (2003),
Targeted deletion reveals an essential function for the telomere length regulator TRF1,
Mol Cell Biol 23, 6533-6541.

De Rycker M, Venkatesan RN, Wei C, Price CM (2003),
Vertebrate tankyrase domain structure and sterile-alpha motif (SAM) mediated multimerization,
Biochem J 372: 87–96.

Bai,Y., and Murnane, J.P. (2003),
Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein,
Human Genetics 113, 337-347.

Karlsreder, J., et al. (2003),
Targeted deletion reveals an essential function for the telomere length regulator TRF1,
Mol. Cell. Biol. 23, 6533-6541 (2003).

Tarsounas, M., Munoz, P., Claas, A., Smiraldo, P.G., Pittman, D.L., Blasco, M.A., and West, S.C. (2004),
Telomere maintenance requires the RAD51D recombination/repair protein,
Cell 117, 337-347.

Smogorzewska, A., and de Lange, T. (2004),
Regulation of telomerase by telomeric proteins,
Annual Review of Biochemistry 73, 177-208.

Undarmaa,B., Kodama, S., Suzuki, K., Niwa, O., and Watanabe, M. (2004),
X-ray induced telomeric instability in Atm-deficient mouse cells,
Biochem. Biophys. Res. Commun. 315, 51-58.

De Rycker M, Price CM (2004),
Tankyrase polymerization is controlled by its sterile alpha motif and poly(ADP-ribose) polymerase domains,
Mol Cell Biol 24: 9802–9812.

Gelmini S, Poggesi M, Distante V, Bianchi S, Simi L, Luconi M, Raggi CC, Cataliotti L, Pazzagli M, Orlando C (2004),
Tankyrase, a positive regulator of telomere elongation, is over expressed in human breast cancer,
Cancer Letters 216: 81–87. [Links/tankyrase 1 inhibitors, Images, Papers, Patents, Books].

Armbruster, B. N., C. M. Linardic, T. Veldman, N. P. Bansal, D. L. Downie, and C. M. Counter (2004),
Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1,
Mol. Cell. Biol. 24:3552-3561.

Wilson, C.G., Maliery, T.J., and Regan, L. (2004),
Detecting protein-protein interactions with GPF-fragment reassembly,
Nat Methods 1, 255-262.

Wong, J.M. and Collins, K. (2004),
Telomere Maintenance and Disease,
Lancet, 362: 983-988.

Tarsounas, M., Munoz, P., Claas, A., Smiraldo, P.G., Pittman, D.L.,
Blasco, M.A., and West, S.C. (2004),
Telomere maintenance requires the RAD51 recombination repair protein,
Cell 117, 337-347.

Bochkarev A, Bochkareva E (2004),
From RPA to BRCA2: lessons from single-stranded DNA binding by the OB-fold,
Curr Opin Struct Biol 2004, 14:36-42.

O'Connor MS, Safari A, Liu D, Qin J, Songyang Z (2004),
The human Rap1 protein complex and modulation of telomere length,
J Biol Chem, 2004, 279:28585-28591.

Dantzer F, Giraud-Panis MJ, Jaco I, Amé JC, Schultz I, Blasco M, Koering CE,
Gilson E, Ménissier-de Murcia J, de Murcia G, Schreiber V (2004),
Functional interaction between poly(ADP-Ribose) polymerase 2 (PARP-2) and TRF2: PARP activity negatively regulates TRF2,
. Mol Cell Biol 2004, 24:1595-1607.

Lei M, Podell ER, Cech TR (2004),
Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection,
Nat Struct Mol Biol 2004, 11:1223-1229.

Dynek JN, Smith S (2004),
Resolution of sister telomere association is required for progression through mitosis,
Science 2004, 304:97-100.

Lillard-Wetherell K, Machwe A, Langland GT, Combs KA, Behbehani GK, Schonberg SA,
German J, Turchi JJ, Orren DK, Groden J (2004),
Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2,
Hum Mol Genet 2004, 13:1919-1932.

Kim SH, Beausejour C, Davalos AR, Kaminker P, Heo SJ, Campisi J (2004),
TIN2 mediates functions of TRF2 at human telomeres,
J Biol Chem 2004, 279:43799-43804.

Ye JZ, Donigian JR, Van Overbeek M, Loayza D, Luo Y, Krutchinsky AN, Chait BT, De Lange T (2004),
TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres,
J Biol Chem 2004, 279:47264-47271.

Ye J.Z., and de Lange, T. (2004),
TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex,
Nature Genetics, 36, 618-623.

d'Adda di Fagagna, SH Teo, SP Jackson (2004),
Functional links between telomeres and proteins of the DNA-damage response,
[direct link] Genes & Development, 18:1781-1799, 2004.

Liu D, O'Connor MS, Qin J, Songyang Z (2004),
Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins,
Journal of Biological Chemistry 2004, 279:51338-51342.

Houghtaling BR, Cuttonaro L, Chang W, Smith S (2004),
A Dynamic Molecular Link between the Telomere Length Regulator TRF1 and the Chromosome End Protector TRF2,
Current Biology, 2004, 14:1621-1631.

Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (2004),
POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex,
Genes and Development, 2004, 18:1649-1654. PIP1 is an alias for TPP1.

Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (2004),
PTOP interacts with POT1 and regulates its localization to telomeres,
Nat Cell Biol 2004, 6:673-680. PTOP is an alias for TPP1.

Smogorzewska A, de Lange T (2004),
Regulation of telomerase by telomeric proteins,
Annual Review of Biochemistry, 73: 177-208.

Seimiya H, Muramatsu Y, Smith S, Tsuruo T (2004),
Functional subdomain in the ankyrin domain of tankyrase 1 required for poly(ADP-ribosyl)ation of TRF1 and telomere elongation,
Mol Cell Biol 24: 1944–1955.

Wang RC, Smogorzewska A, de Lange T (2004),
Homologous recombination generates T-loop-sized deletions at human telomeres.
Cell 2004, 119:355-368.

Ye, J. Z.-S., Hockemeyer, D., Krutchinsky, A. N., Loayza, D., Hooper, S. M., Chait, B. T., de Lange, T. (2004).
POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex,
Genes and Development 18: 1649-1654. PIP1 is an alias for TPP1.

Du, X, Shen, J, Kugan, N, Furth, E.E., Lombard, D.B., Cheung, C,
Pak, S, Luo, G, Pignolo, R.J, DePinho, R.A., Guarente, L, and Johnson, F.B. (2004),
Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes,
Mol Cell Biol, 24: 8437-8446.

Chang, S., Multani, A.S., Cabrera, N.G., Naylor, M.L., Laud, P., Lombard, D., Pathak, S.,
Guarente, L., and DePinho, R.A. (2004),
Essential role of limiting telomeres in the pathogenesis of Werner syndrome,
Nature Genetics 36, 877-882, Epub 2004 July 2004.

Li, B., Navarro, S., Kasahara, N., and Comai, L. (2004),
Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1,
Journal of Biological Chemistry 279, 13659-13667.

Opresko, P.L., Otterlei, M., Graakjaer, J., Bruheim, P.
Dawut, L, Kolvraa, S., May, A., Seidmann, M.M., and Bohr, V.A. (2004),
The Werner Syndrome Helicase and Exonuclease Cooperate to Resolve Telomeric D Loops in a Manner Regulated by TRF1 and TRF2,
Mol Cell 14, 763-774.

Loayza, D., H. Parsons, J. Donigian, K. Hoke, and T. de Lange (2004),
DNA binding features of human POT1: a nonamer 5'-TAGGGTTAG-3' minimal binding site, sequence specificity, and internal binding to multimeric sites,
Journal of Biological Chemistry, 279:13241-13248.

Veldman, T., K. T. Etheridge, and C. M. Counter (2004),
Loss of hPot1 function leads to telomere instability and a cut-like phenotype,
Curr. Biol, 14:2264-2270.

Crabbe, L, Verdun, R.E., Haggblom, C.I., and Karlsreder, J. (2004),
Defective telomere lagging strand synthesis in cells lacking WRN helicase activity,
Science 306, 1951-1953.

Hanaoka, S., Nagaoi, A., and Nishimura, Y. (2005),
Comparison between TRF2 and TRF1 of their telomeric DNA-bound structures and DNA-binding activities,
Protein Science 14: 199-130.

Court, R., Chapman, L., Fairall, L., and Rhodes, D. (2005),
How the human telomeric proteins TRF1 and TRF2 recognize telomeric DNA: A view from high-resolution crystal structures,
EMBO Rep. 6: 39-45.

Gang Liu, June Chunqiu Hou, Robert T. Watson, and Jeffrey E. Pessin (2005),
Initial entry of IRAP into the insulin-responsive storage compartment occurs prior to basal or insulin-stimulated plasma membrane recycling,
American Jounal of Physiology Endocrinology and Metabolism November 2005, vol. 289, no. 5, E746-E752.
Tankyrase 1 interacts with IRAP.

Yang, Q., Zheng, Y.L., and Harris C.C. (2005),
POT1 and TRF2 cooperate to maintain telomeric integrity,
Mol Cell Biol, 25, 1070-1080.

Bunch, J. T., N. S. Bae, J. Leonardi, and P. Baumann (2005),
Distinct requirements for pot1 in limiting telomere length and maintaining chromosome stability,
Mol. Cell. Biol, 25:5567-5578.

Yang, Q., Zheng, Y.L., and Harris, C.C. (2005),
POT1 and TRF2 Cooperate to Maintain Telomeric Integrity,
Mol Cell Biol 25, 1070-1080.

Opresko, P. L., Mason, P. A., Podell, E. R., Lei, M., Hickson, I. D., Cech, T. R., Bohr, V. A. (2005),
POT1 Stimulates RecQ Helicases WRN and BLM to Unwind Telomeric DNA Substrates,
Journal of Biological Chemistry 280: 32069-32080.

Shakirov, E. V., Surovtseva, Y. V., Osbun, N., Shippen, D. E. (2005),
The Arabidopsis Pot1 and Pot2 Proteins Function in Telomere Length Homeostasis and Chromosome End Protection,
Molecular and Cellular Biology, 25: 7725-7733.

de Lange T (2005),
Shelterin: the protein complex that shapes and safeguards human telomeres,
Genes and Development, 2005, 19:2100-2110.

Chang P, Coughlin M, Mitchison TJ (2005),
Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function,
Nat Cell Biol 2005, 7:1133-1139. See TA/Tankyrase.

Bradshaw PS, Stavropoulos DJ, Meyn MS (2005),
Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage,
Nature Genetics 2005, 37:193-197.

Zaug AJ, Podell ER, Cech TR (2005),
Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro,
Proc Natl Acad Sci USA 2005, 102:10864-10869.

Bradshaw PS, Stavropoulos DJ, Meyn MS (2005),
Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage,
Nature Genetics 2005, 37:193-197.

Kaminker P, Plachot C, Kim SH, Chung P, Crippen D, Petersen OW, Bissell MJ, Campisi J, Lelievre SA (2005),
Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2,
J Cell Sci 2005, 118:1321-1330.

Verdun RE, Crabbe L, Haggblom C, Karlseder J (2005),
Functional human telomeres are recognized as DNA damage in G2 of the cell cycle,
Mol Cell 2005, 20:551-561.

Shakirov EV, Surovtseva YV, Osbun N, Shippen DE (2005),
The Arabidopsis Pot1 and Pot2 proteins function in telomere length homeostasis and chromosome end protection,
Mol Cell Biol 2005, 25:7725-7733.

Wright, W.E., and Shay, J.W. (2005),
Telomere-binding factors and general DNA repair,
Nature Genetics, 37: 116-118.

Kelleher, C., I. Kurth, and J. Lingner (2005),
Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro,
Mol. Cell. Biol, 25:808-818.

Lei, M., A. J. Zaug, E. R. Podell, and T. R. Cech. (2005),
Switching human telomerase on and off with hPOT1 protein in vitro,
Journal of Biological Chemistry, 280:20449-20456.

Hiroyuki Seimiya, Yukiko Muramatsu, Tomokazu Ohishi, and Takashi Tsuruo (2005),
Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics,
Cancer Cell, Vol.7, issue 1, January 2005, pp.25-37. See also TA/Tankyrase.

Hockemeyer, D., Sfeir, A.J., Shaw, J.W., Wright, W.E., and de Lange, T. (2005),
POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes end,
EMBO Journal 24, 2667-2678.

Celli, G.B., and de Lange, T. (2005),
DNA processing not required for ATM-mediated telomere damage response after TRF2 deletion,
Nature Cell Biology 7, 712-718.

Rhodes, D. (2005),
The structural biology of telomeres,
In Telomeres (eds de Lange, T. et al.) pp. 317-344.
Cold Spring Harbor Laboratory Press, Cold Spring Harbor,N.Y.

Miller, K.M., Rog, O., and Cooper, J.P. (2006),
Semiconservative DNA replication through telomeres requires TAZ1,
Nature, 440, 824-828. Taz1 is a fission yeast telomeric protein.

Songyang, Z. and Liu, D. (2006)
Inside the mammalian telomere interactome: regulation and regulatory activities of telomeres,
Critical Review of Eucaryotic Gene Expression, 16, 103-118.

O'Connor, M.S., Safari, A., Xin, H., Liu, D., and Songyang, Z. (2006),
A critial role for TPP1 and TIN2 interaction in higher-order telomeric complex assembly,
PNAS USA 103, 11874-11879.

Dimitrova, N. and de Lange, T. (2006),
MDC1 accelerates non-homologous end-joining of dysfunctional telomeres,
Genes and Development 20: 3238-3243.

H. Seimiya (2006),
The telomeric PARP, tankyrases, as targets for cancer therapy,
British Journal of Cancer (2006) 94, 341–345. Describes tankyrase 1 phosphorylation in insulin-stimulated cells, ect.

Celli, G.B., Lazzerini Denchi, E., and de Lange, T. (2006),
Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination,
Nature Cell Biology.

Freibaum, B. D., and C. M. Counter (2006),
hSnm1B is a novel telomere-associated protein,
Journal of Biological Chemistry, 281:15033-15036.

Hockemeyer D, Daniels JP, Takai H, de Lange T (2006),
Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres,
Cell 2006, 126:63-77.

Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, Bachilo O,
Pathak S, Tahara H, Bailey SM, Deng Y, Behringer RR, Chang S (2006),
Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres,
Cell 2006, 126:49-62.

Churikov D, Wei C, Price CM (2006),
Vertebrate POT1 restricts G-overhang length and prevents activation of a telomeric DNA damage checkpoint but is dispensable for overhang protection,
Mol Cell Biol 2006, 26:6971-6982.

Gomez M, Wu J, Schreiber V, Dunlap J, Dantzer F, Wang Y, Liu Y (2006),
PARP1 Is a TRF2-associated Poly(ADP-Ribose)Polymerase and Protects Eroded Telomeres,
Mol Biol Cell 2006, 17:1686-1696.

Verdun RE, Karlseder J (2006),
The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres,
Cell 2006, 127:709-720.

Zhu Q, Yasumoto H, Tsai RY (2006),
Nucleostemin Delays Cellular Senescence and Negatively Regulates TRF1 Protein Stability,
Mol Cell Biol 2006, 26:9279-9290.

Lee TH, Perrem K, Harper JW, Lu KP, Zhou XZ (2006),
The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance,
J Biol Chem 2006, 281:759-768.

Ling Wu, Asha S. Multani, Hua He, Wilfredo Cosme-Blanco, Yu Deng, Jian Min Deng,
Olga Bachilo, Sen Pathak, Hidetoshi Tahara, Susan M. Bailey, Yibin Deng, Richard R. Behringer and Sandy Chang (2006),
Pot1 Deficiency Initiates DNA Damage Checkpoint Activation and Aberrant Homologous Recombination at Telomeres,
Cell, Volume 126, Issue 1, 14 July 2006, Pages 49-62.

Kristine Kelly, (2006),
Evidence of rapid evolution is found at the tips of chromosomes,
Rockefeller Newswire.

Songyang Z, Liu D (2006),
Inside the mammalian telomere interactome: regulation and regulatory activities of telomeres,
Crit Rev Eukaryot Gene Expr 2006, 16:103-118.

Fouche N, Cesare AJ, Willcox S, Ozgur S, Compton SA, Griffith JD (2006),
The basic domain of TRF2 directs binding to DNA junctions irrespective of the presence of TTAGGG repeats,
J Biol Chem 2006, 281:37486-37495.

Baumann P (2006),
Are mouse telomeres going to pot?,
Cell 2006, 126:33-36.

Atanasiu C, Deng Z, Wiedmer A, Norseen J, Lieberman PM (2006),
ORC binding to TRF2 stimulates OriP replication,
EMBO Rep 2006, 7:716-721.

O'Connor MS, Safari A, Xin H, Liu D, Songyang Z (2006),
A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly,
Proc Natl Acad Sci USA 2006, 103:11874-11879.

He H, Multani AS, Cosme-Blanco W, Tahara H, Ma J, Pathak S, Deng Y, Chang S (2006),
POT1b protects telomeres from end-to-end chromosomal fusions and aberrant...
(mouse genome; code-scrambled reference, scrambled part removed).

See Zhong Deng, Jayaraju Dheekollu, Dominique Broccoli, Anindya Dutta, and Paul Lieberman (2007),
The Origin Recognition Complex Localizes to Telomere Repeats and Prevents Telomere-Circle Formation,
Current Biology 17, Nov.20,2007.

Denchi, E.L., and de Lange, T. (2007),
Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1,
Nature 448, 1068-1071.

Songyang Z (2007),
TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase,
Nature 2007, 445:559-562.

Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M (2007),
The POT1-TPP1 telomere complex is a telomerase processivity factor,
Nature 2007, 445:506-510.

Potts PR, Yu H (2007),
The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins,
Nat Struct Mol Biol 2007, 14:581-590.

Wu Y, Xiao S, Zhu XD (2007),
MRE11-RAD50-NBS1 and ATM function as co-mediators of TRF1 in telomere length control,
Nat Struct Mol Biol 2007, 14:832-840.

Blasco MA (2007),
The epigenetic regulation of mammalian telomeres,
Nat Rev Genet 2007, 8:299-309.

Verdun RE, Karlseder J (2007),
Replication and protection of telomeres,
Nature 2007, 447:924-931.

Amiard S, Doudeau M, Pinte S, Poulet A, Lenain C, Faivre-Moskalenko C,
Angelov D, Hug N, Vindigni A, Bouvet P, Paoletti J, Gilson E, Giraud-Panis MJ (2007),
A topological mechanism for TRF2-enhanced strand invasion,
Nat Struct Mol Biol 2007, 14:147-154.

Hiroshi Aoki, Eiji Iwado, Mark S. Eller, Yasuko Kondo, Keishi Fujiwara, Guang-Zhi Li, Kenneth R. Hess,
Doris R. Siwak, Raymond Sawaya, Gordon B. Mills, Barbara A. Gilchrest and Seiji Kondo (2007).
Telomere 3' overhang-specific DNA oligonucleotides induce autophagy in malignant glioma cells,
The FASEB Journal 2007;21:2918-2930.

Qin Yang, Ran Zhang, Izumi Horikawa, Kaori Fujita, Yalda Afshar,
Antti Kokko, P ivi Laiho, Lauri A. Aaltonen and Curtis C. Harris (2007),
Functional Diversity of Human Protection of Telomeres 1 Isoforms in Telomere Protection and Cellular Senescence,
Cancer Research 67, 11677-11686, December 15, 2007.

Martin V, Du LL, Rozenzhak S, Russell P (2007),
Protection of telomeres by a conserved Stn1-Ten1 complex,
Proc Natl Acad Sci USA 2007, 104:14038-14043.

Gao H, Cervantes RB, Mandell EK, Otero JH, Lundblad V (2007),
RPA-like proteins mediate yeast telomere function,
Nat Struct Mol Biol 2007, 14:208-214.

Chen LY, Liu D, Songyang Z (2007):
Telomere maintenance through spatial control of telomeric proteins,
Mol Cell Biol 2007, 27:5898-5909.

Lamesh, P., Li, N., Milstein, S., Fan, C., Hao, T., Szabo, G., Hu, Z., Venkatesan, K., Bethel, G., Martin, P.,
Rogers, J., Lawlor, s., McLaren, S., Dicrot, A., Borick, H., Cusick, M.E., Vandenhaute, J.,
Dunham, I., Hill, D.E., and Vidal, M. (2007),
hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes,
Genomics 89, 307-315.

Canudas, S., Houghtaling, B.R., Kim, J.Y., Dynek, J.N., Chang, W.G., and Smith, S. (2007),
Protein requirements for sister telomere association in human cells,
EMBO Journal 26, 4867-4878.

Hockemeyer, D., W. Palm, T. Else, J. P. Daniels, K. K. Takai, J. Z. Ye, C. E. Keegan, T. de Lange, and G. D. Hammer (2007),
Telomere protection by mammalian Pot1 requires interaction with Tpp1,
Nature Structural and Molecular Biology, 14:754-761.

Xin, H., Liu, D., Wan, M., Safari, A., Kim, H., Sun, W., O'Connor M, S., and Songyang, Z. (2007),
TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase,
Nature 445, 559-562.

Else, T., et al. (2008),
TPP1/Acd maintains genomic stability through a complex role in telomere protection,
Chromosome Research 15, 1001-1013.

Xin, H, Liu, D, Songyang, Z (2008),
The telosome/shelterin complex and its functions,
Genome Biology 9: 232.

Etheridge, K. T., S. A. Compton, K. S. Barrientos, S. Ozgur, J. D. Griffith, and C. M. Counter (2008),
Tethering telomeric double- and single-stranded DNA-binding proteins inhibits telomere elongation,
Journal of Biological Chemistry, 283:6935-6941.

Barrientos, K. S., M. F. Kendellen, B. D. Freibaum, B. N. Armbruster, K. T. Etheridge, and C. M. Counter (2008),
Distinct functions of POT1 at telomeres, Mol. Cell. Biol, 28:5251-5264.

Hu CD, Kerppola TK (2008),
Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis,
Nature Biotechnology 2003, 21:539-545.

Miyoshi T, Kanoh J, Saito M, Ishikawa F (2008),
Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length,
Science 2008, 320:1341-1344.

Lee J, Mandell EK, Tucey TM, Morris DK, Lundblad V (2008),
The Est3 protein associates with yeast telomerase through an OB-fold domain,
Nature Structural and Molecular Biology 2008, 15:990-997.

Young Yu E, Wang F, Lei M, Lue NF (2008),
A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3,
Nat Structural and Molecular Biology 2008, 15:985-989.

Longhese MP (2008),
DNA damage response at functional and dysfunctional telomeres,
Genes and Developement 2008, 22:125-140.

Chen Y, Yang Y, van Overbeek M, Donigian JR, Baciu P, de Lange T, Lei M (2008),
A Shared Docking Motif in TRF1 and TRF2 Used for Differential Recruitment of Telomeric Proteins,
Science 2008, 319:1092-1096.

Tarassov, K., Messier, V., Landry, C.R., Radinovic, S., Serna Molina, M.M., Shames, I.,
Malitskaya, Y., Vogel, J., Bussey, H., and Michnick, S.W. (2008),
An in vivo map of the yeast protein interactome,
Science 320, 1465-1470.

Kim, S.H., Davalos, A.R., Heo, S.J., Rodier, F., Zou, Y.,
Beausejour, C., Kaminker, P., Yannone, S.M., and Campisi, J. (2008),
Telomere dysfunction and cell survival: roles for distinct TIN2-containing complexes,
Journal of Cell Biology 181, 447-460.

Tsangarts, E., et. al, (2008),
Ataxia and pancytopenia caused by a mutation in TINF2,
Human Genetics, 124, 507-513.

Raynaud, C. M., L. Sabatier, O. Philipot, K. A. Olaussen, and J. C. Soria (2008),
Telomere length, telomeric proteins and genomic instability during the multistep carcinogenic process,
Crit. Rev. Oncol. Hematol, 66:99-117.

Palm, W. and de Lange, T. (2008),
How shelterin protects mammalian telomeres,
Annual Review of Genetics 42, 301-334.

Agnel Sfeir, Settapong T. Kosiyatrakul, Dirk Hockemeyer, Sheila L. MacRae, Jan Karlseder,
Carl L. Schildkraut and Titia de Lange (2009),
Mammalian Telomeres Resemble Fragile Sites and Require TRF1 for Efficient Replication,
Cell 138, 90-103, July 10, 2009.

Kim, H., Lee, O.H., Xin, H., Chen, L.Y., Qin, J.,
Chae, H.K., Lin, S.Y., Safari, A., Liu, D., and Songyang, Z. (2009),
TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs,
Nature Structural Molecular Biology 16, 372-379.

Peng, G., Lin, S.Y. (2009),
BRIT1/MCPH1 is a multifunctional DNA damage responsive protein mediating DNA repair-associated chromatin remodeling,
Cell Cycle 8.

Kendellen, M. F., Barrientos, K. S., Counter, C. M. (2009),
POT1 Association with TRF2 Regulates Telomere Length,
Mol. Cell. Biol. 29: 5611-5619.

Oganesian, L., Karlseder, J. (2009),
Telomeric armor: the layers of end protection,
Journal of Cell Science 122: 4013-4025.

Mitchell, T. R. H., Glenfield, K., Jeyanthan, K., Zhu, X.-D. (2009),
Arginine Methylation Regulates Telomere Length and Stability,
Mol. Cell. Biol. 29: 4918-4934.

Dejardin, J., and Kingston, R.E. (2009),
Purification of proteins associated with specific genomic Loci,
Cell 136, 175-186.

Marco Folinia, Paolo Gandellinia and Nadia Zaffaroni (2009),
Targeting the telosome: Therapeutic implications,
Biochimica et Biophysica Acta, April 2009, 309-316. See lifexnotes5.html (Telomeric Proteins Nomenclature) notes.

Kaminker PG, Kim SH, Desprez PY, Campisi J. (2009),
A novel form of the telomere-associated protein TIN2 localizes to the nuclear matrix,
Cell Cycle 2009: 8: 931–939.

de Lange, T. (2009),
How telomeres solve the end-protection problem,
Science 326, 948-952.

Abreu, E., Aritonovska, E., Reichenbach, P., Cristofari, G., Culp, B., Terns, R. M., Lingner, J., Terns, M. P. (2010),
TIN2-Tethered TPP1 Recruits Human Telomerase to Telomeres In Vivo,
Mol Cell Biol. 30: 2971-2982.

Lee, J., Mandell, E. K., Rao, T., Wuttke, D. S., Lundblad, V. (2010),
Investigating the role of the Est3 protein in yeast telomere replication.
Nucleic Acids Research 38: 2279-2290.

Ok-Hee Lee, Hyeung Kim, Quanyuan He, Hwa Jin Baek, Dong Yang, Liuh-Yow Chen,
Jiancong Liang, Heekyung Kate Chae, Amin Safari, Dan Liu and Zhou Songyang (2011),
Genome-wide YFP Fluorescence Complementation Screen Identifies New Regulators for Telomere Signaling in Human Cells,
Molecular and Cellular Proteomics, 2011, 10, M110.001628.

Paula Martinez and Maria A. Blasco (2010),
Role of shelterin in cancer and aging, Aging Cell 9, 653-666.

Paula Martinez and Maria A. Blasco (2011),
Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins,
Nature Reviews Cancer, vol. 11, March 2011, 161-176.

Sichun Lin (2011),
Analysis of the Role of TRF1 and SMG6 in Telomere Length Maintenance, MS Thesis, McMaster University. [Index/hEST1A].

Music: Jesse by Carly Simon.

POT1 papers

Ye, J. Z.-S., Hockemeyer, D., Krutchinsky, A. N., Loayza, D., Hooper, S. M., Chait, B. T., de Lange, T. (2004),
POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex,
Genes and Development 18: 1649-1654.

Shakirov, E. V., Surovtseva, Y. V., Osbun, N., Shippen, D. E. (2005),
The Arabidopsis Pot1 and Pot2 Proteins Function in Telomere Length Homeostasis and Chromosome End Protection,
Molecular and Cellular Biology, 25: 7725-7733.

Opresko, P. L., Mason, P. A., Podell, E. R., Lei, M., Hickson, I. D., Cech, T. R., Bohr, V. A. (2005),
POT1 Stimulates RecQ Helicases WRN and BLM to Unwind Telomeric DNA Substrates,
Journal of Biological Chemistry 280: 32069-32080.

Kendellen, M. F., Barrientos, K. S., Counter, C. M. (2009),
POT1 Association with TRF2 Regulates Telomere Length,
Mol. Cell. Biol. 29: 5611-5619.

________7.9 Telomerase Functional Environment [Links, Images, Video, Papers, Books; Index/Telosome].

J. Roy, T.B. Fulton, and Elizabeth H. Blackburn (1998). Specific telomerase RNA residues distant from the template are essential for telomerase function. Genes and Development 12, 3286-3300.

A. Ray and K.W. Runge (1999). The yeast telomere length counting machinery is sensitive to sequences at the telomere-nontelomere junction. Molecular and Cellular Biology 19, 31-45.

Shawn E. Holt, Dara L. Aisner, Joseph Baur, Valerie M. Tesmer, Marife Dy, Michel Oullette, James B. Trager,
Gregg B. Morin, David O. Toft, Jerry W. Shay, Woodring E. Wright, and Michael A. White (1999),
Functional requirement of p23 and Hsp90 in telomerase complexes,
Genes and Development 1999 13: 817-826.

J.C. Prescott and Elizabeth H. Blackburn (2000). Telomerase template mutations reveal sequence-specific requirements for the activation and repression of telomerase action at telomeres. Molecular and Cellular Biology 20, 2941-2948.

Etheridge, K.T., S.S.Banik, B.N.Armbruster, Y. Zhu, R. M. Terns, M.P. Turns, and C.M.Counter (2002), The nucleolar localization domain of the catalytic unit of human telomerase,
J. Biol. Chem. 15:15.

Brian R. Keppler, Allen T. Grady, and Michael B. Jarstfer (2006),
The Biochemical Role of the Heat Shock Protein 90 Chaperone Complex in Establishing Human Telomerase Activity,
The Journal of Biological Chemistry 281, No.29, 19840-19848.

Eva Sykorova and Jiri Fajkus (2009), Structure-Function relationships in Telomerase Genes, Biol. Cell (2009).101, 375-392.

Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE, (2009). A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis, Science (2009). Identifies the roles of dyskerin [Links] and TCAB1 [Links] in detailed telomerase activity, and includes an analysis of other important factors.

________7.10 Telomerase and Protection of Mitochondrial DNA [Links, Images, Video, Papers, Books].

Zhang, P., Chan, S.L., Fu, W., Medoza, M., and Mattson, M.P. (2003),
TERT suppresses apoptosis at a premitochondrial step by a mechanism requiring reverse transcriptase activity and 14-3-3 protein binding ability, FASEB Journal 17, 767-769.

Haendeler, J. et al. (2004), Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells, Circulation Research 94, 768-775.

Santos, J.H., Meyer, J.N., Skorvaga, M., Annab, L.A., and Van Houten, B. (2004), Mitochondrial hTERT exacerbates free-radical mediated mtDNA damage, Aging Cell 3, 399-411.

Santos, J.H., Meyer, J.N., and Van Houten, B. (2006), Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis, Human Molecular Genetics 15, 1757-1768.

Massard, C., et al. (2006), hTERT: a novel endogenous inhibitor of the mitochondrial cell death pathway, Oncogene 27, 3754-3760.

Lee, J., et al. (2008), TERT promotes cellular and organismal survival independently of telomerase activity, Oncogene 27, 3754-3760.

Haendeler J, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S, et al., (2009),
Mitochondrial telomerase reverse transcriptase [?] binds to and protects mitochondrial DNA and function from damage,
Arterioscler. Thromb. Vasc. Biol. (2009). "Mitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing respiratory chain activity and protecting against oxidative stress-induced damage."

______7.11 Measuring Telomere Length [lifexlabs/Telomeasures, LifexLabs/Telomeasures, Links, Images, Video, Papers, Books].

_________7.11.1 Measuring Telomere Length with PCR Methods (Cawthon).
__________[LifexLabs/Telomeasures, Links, Images, Video, Papers, Books].

Marcel E. Gil and Thérèsa L. Coetzer, (2004). Real-time quantitative PCR of telomere length, Molecular Biotechnology, Volume 27, Number 2, June, 2004.

(2008), Biotechniques.com/A quantitative real-time PCR method for absolute telomere length.

Richard M. Cawthon (2009), Telomere length measurement by a novel monochrome multiplex quantitative PCR method, Nucleic Acids Research, 2009 February; 37(3)

_________7.11.2 Measuring with Southern blot analysis of telomere restriction fragments.
__________[LifexLabs/Telomeasures, Links, Images, Video, Papers, Books].

_________7.11.3 Measuring with Quantitative fluorescence in situ hybridization with digital fluorescence microscopy (Q-FISH).
__________[LifexLabs/Telomeasures, Links, Images, Video, Papers, Books].

Canela A, Vera E, Klatt P, Blasco MA (2007),
High-throughput telomere length quantification by FISH and its application to human population studies,
PNAS USA, 2007 Mar 27; 104(13):5300-5.

_________7.11.4 Measuring with Quantitative fluorescence in situ hybridization with flow cytometry (flow-FISH).
__________[LifexLabs/Telomeasures, Links, Images, Video, Papers, Books].

_________7.11.5 Measuring with Quantitative fluorescent in situ hybridization laser scanning cytometry (Q-FISHLSC).
__________[LifexLabs/Telomeasures, Links, Images, Video, Papers, Books].