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Cited by 610

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Senescence and immortalization: role of telomeres and telomerase

Shay, Jerry W., Wright, Woodring E.·2005·Carcinogenesis
DOI 10.1093/carcin/bgh296
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Abstract

Telomere dynamics are a critical component of both aging and cancer. Telomeres progressively shorten in almost all dividing cells and most human cells do not express or maintain sufficient telomerase activity to fully maintain telomeres. There is accumulating evidence that when only a few telomeres are short, they form end-associations, leading to a DNA damage signal resulting in replicative senescence (a cellular growth arrest, also called the M1 stage). In the absence of cell-cycle checkpoint pathways (e.g. p53 and or p16/Rb), cells bypass M1 senescence and telomeres continue to shorten eventually resulting in crisis (also called the M2 stage). M2 is characterized by many 'uncapped' chromosome ends, end-fusions, chromosome breakage fusion-bridge cycles, mitotic catastrophe and a high fraction of apoptotic cells. In a rare M2 cell, telomerase (a cellular reverse transcriptase) can be reactivated or up-regulated, resulting in indefinite cell proliferation. This cellular immortalization is a potentially rate-limiting step in carcinogenesis that is important for the continuing evolution of most advanced cancers. In this perspective we will present our views on the evidence for telomere dysfunction in aging and in cancer progression. We will argue that telomere shortening in the absence of other alterations may be a potent tumor suppressor mechanism and we will discuss the evidence for and against the major molecular mechanisms proposed to initiate replicative senescence.

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Research works printed but not linked: 95

  1. Vogelstein,B. and Kinzler,K.W. ( 1993 ) The multistep nature of cancer. Trends Genet. , 9 , 138 –141. · DOI
  2. Faragher,R.G.A. and Kipling,D. ( 1998 ) How might replicative senescence contribute to human ageing? BioEssays , 20 , 985 –991. · DOI
  3. Kapahi,P., Boulton,M.E. and Kirkwood,T.B. ( 1999 ) Positive correlation between mammalian life span and cellular resistance to stress. Free Radic. Biol. Med. , 26 , 495 –500. · DOI
  4. Hayflick,L. ( 1980 ) Cell aging. In Eisdorfer,C. (ed.) Annual Review of Gerontology and Geriatrics . Springer Publishing Co., New York, Vol. 1, pp. 26–67.
  5. Hayflick,L. and Moorhead,P.S. ( 1961 ) The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. , 25 , 585 –621. · DOI · Paper page
  6. Rubin,H. ( 1997 ) Cell aging in vivo and in vitro . Mech. Ageing Dev. , 98 , 1 –35. · DOI
  7. Wright,W.E. and Shay,J.W. ( 1992 ) The two-stage mechanism controlling cellular senescence and immortalization. Exp. Gerontol. , 27 , 383 –389. · DOI · Paper page
  8. Wright,W.E. and Shay,J.W. ( 2002 ) Historical claims and current interpretations of replicative aging. Nat. Biotechnol. , 20 , 682 –688. · DOI
  9. Wong,K.K. and DePinho,R.A. ( 2003 ) Walking the telomere plank into cancer. J. Natl Cancer Inst. , 95 , 1184 –1186. · DOI
  10. Meeker,A.K. and De Marzo,A.M. ( 2004 ) Recent advances in telomere biology: implications for human cancer. Curr. Opin. Oncol. , 16 , 32 –38. · DOI · Paper page
  11. Meeker,A.K., Hicks,J.L., Iacobuzio-Donahue,C.A., Montgomery,E.A., Westra,W.H., Chan,T.Y., Ronnett,B.M. and De Marzo,A.M. ( 2004 ) Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis. Clin. Cancer Res. , 10 , 317 –326. · DOI · Paper page
  12. Sharpless,N.E. and DePinho,R.A. ( 2004 ) Telomeres, stem cells, senescence and cancer. J. Clin. Invest. , 113 , 160 –168. · DOI
  13. Benetos,A., Okuda,K., Lajemi,M., Kimura,M., Thomas,F., Skurnick,J., Lobat,C., Bean,K. and Aviv,A. ( 2001 ) Telomere length as an indicator of biologic aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension , 37 , 381 –385. · DOI
  14. Brouilette,S., Singh,R.K., Thompson,J.R., Goodall,A.H. and Samani,N.J. ( 2003 ) White cell telomere length and risk of premature myocardial infarction. Arterioscler. Thromb. Vasc. Biol. , 23 , 842 –846. · DOI · Paper page
  15. Okuda,K., Bardequez,A., Gardner,J.P., Rodriguez,P., Ganesh,V., Kimura,M., Skurnick,J., Awad,G. and Aviv,A. ( 2002 ) Telomere length in the newborn. Pediat. Res. , 52 , 377 –381. · DOI · Paper page
  16. Graakjaer,J., Bischoff,C., Korsholm,L., Holstebroe,S., Vach,W., Bohr,V.A., Christensen,K. and Kolvraa,S. ( 2003 ) The pattern of chromosome-specific variations in telomere length in humans is determined by inherited, telomere-near factors and is maintained throughout life. Mech. Ageing Dev. , 124 , 629 –640. · DOI
  17. Mitchell,J.R., Wood,E. and Collins,K. ( 1999 ) A telomerase component is defective in the human disease dyskeratosis congenita. Nature , 402 , 551 –555. · DOI · Paper page
  18. Shay,J.W. and Wright,W.E. ( 1999 ) Mutant dyskerin ends relationship with telomerase. Science , 286 , 2284 –2285. · DOI
  19. Wong,J.M. and Collins,K. ( 2003 ) Telomere maintenance and disease. Lancet , 362 , 983 –988. · DOI
  20. Shay,J.W. and Wright,W. E. ( 2004 ) Telomeres in dyskeratosis congenita Nature Genet. , 36 , 437 –438. · DOI
  21. Wu,X. Amos,C.I., Zhu,Y., Zhao,H., Grossman,B.H., Shay,J.W., Swan,G.E., Benowitz,N.L., Luo,S. and Spitz,M.R. ( 2003 ) Telomere dysfunction: a potential cancer predisposition factor. J. Natl. Cancer Inst. , 95 , 1211 –1218. · DOI
  22. Samani,N.J., Boultby,R., Butler,R., Thompson,J.R. and Goodall,A.H. ( 2001 ) Telomere shortening in atherosclerosis. Lancet , 358 , 472 –473. · DOI · Paper page
  23. Obana,N., Takagi,S., Kinouchi,Y. et al . ( 2003 ) Telomere shortening of peripheral blood mononuclear cells in coronary disease patients with metabolic disorders. Intern. Med. , 42 , 150 –153. · DOI
  24. Hastie,N.D., Dempster,M., Dunlop,M.G., Thompson,A.M., Green,D.K. and Allshire,R.C. ( 1990 ) Telomere reduction in human colorectal carcinoma and with aging. Nature , 346 , 866 –868. · DOI · Paper page
  25. Yan,P., Saraga,E.P., Bouzourene,H., Bosman,F.T. and Benhattar,J. ( 1999 ) Telomerase activation in colorectal carcinogenesis. J. Pathol. , 189 , 207 –212. · DOI
  26. Allshire,R.C., Dempster,M. and Hastie,N.D. ( 1989 ) Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic Acids Res. , 17 , 4611 –4627. · DOI
  27. Baird,D.M., Coleman,J., Rosser,Z.H. and Royle,N.J. ( 2000 ) High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: implications for telomere biology and human evolution. Am. J. Hum. Genet. , 66 , 235 –250. · DOI
  28. Blackburn,E.H. ( 2001 ) Switching and signaling at the telomere. Cell , 106 , 661 –673. · DOI
  29. Blasco,M. ( 2004 ) Telomere epigenetics: a higher-order control of telomere length in mammalian cells. Carcinogenesis , 25 , 1083 –1087. · DOI
  30. Blasco,M.A. ( 2003 ) Mammalian telomeres and telomerase: why they matter for cancer and aging. Eur. J. Cell Biol. , 82 , 441 –446. · DOI
  31. der-Sarkissian,H., Bacchetti,S., Cazes,L. and Londono-Vallejo,J.A. ( 2004 ) The shortest telomeres drive karyotype evolution in transformed cells. Oncogene , 23 , 1221 –1228. · DOI
  32. Ferreira,M.G., Miller,K.M. and Cooper,J.P. ( 2004 ) Indecent exposure: when telomeres become uncapped. Mol. Cell , 13 , 7 –18. · DOI
  33. Goytisolo,F.A. and Blasco,M.A. ( 2002 ) Many ways to telomere dysfunction: in vivo studies using mouse models. Oncogene , 21 , 584 –591. · DOI
  34. Griffith,J.D., Comeau,L., Rosenfield,S., Stansel,R.M., Bianchi,A., Moss,H. and de Lange,T. ( 1999 ) Mammalian telomeres end in a large duplex loop. Cell , 97 , 503 –514. · DOI · Paper page
  35. Greider,C.W. ( 1990 ) Telomeres, telomerase and senescence. Bioessays , 12 , 363 –369. · DOI
  36. Greider,C.W. and Blackburn,E.H. ( 1985 ) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell , 43 , 405 –413. · DOI · Paper page
  37. Harley,C.B. ( 1991 ) Telomere loss: mitotic clock or genetic time bomb? Mutat. Res. , 256 , 271 –282. · DOI · Paper page
  38. Harrington,L. ( 2004 ) Those damaged telomeres! Curr. Opin. Genet. Dev. , 14 , 22 –28. · DOI
  39. Huffman,K.E., Levene,S.D., Tesmer,V.M., Shay,J.W. and Wright,W.E. ( 2000 ) Telomere shortening is proportional to the size of the G-rich telomeric 3′-overhang. J. Biol. Chem. , 275 , 19719 –19722. · DOI
  40. Keys,B., Serra,V., Saretzki,G. and von Zglinicki,T. ( 2004 ) Telomere shortening in human fibroblasts is not dependent on the size of the telomeric-3′-overhang. Aging Cell , 3 , 103 –109. · DOI
  41. Levy,M.Z., Allsopp,R.C., Futcher,A.B., Greider,C.W. and Harley,C.B. ( 1992 ) Telomere end-replication problem and cell aging. J. Mol. Biol. , 225 , 951 –960. · DOI · Paper page
  42. Londono-Vallejo,J.A., DerSarkissian,H., Cazes,L. and Thomas,G. ( 2001 ) Differences in telomere length between homologous chromosomes in humans. Nucleic Acids Res. , 29 , 3164 –3171. · DOI
  43. Moyzis,R.K., Buckingham,J.M., Cram,L.S. et al . ( 1988 ) A highly conserved repetitive DNA sequence, (TTAGGG) n , present at the telomeres of human chromosomes. Proc. Natl Acad. Sci. USA , 85 , 6622 –6626. · DOI · Paper page
  44. Olovnikov,A.M. ( 1973 ) A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J. Theoret. Biol. , 41 , 181 –190. · DOI
  45. Suda,T., Fujiyama,A., Takimoto,M., Igarashi,M., Kuroiwa,T., Waguri,N., Kawai,H., Mita,Y. and Aoyagi,Y. ( 2002 ) Interchromosomal telomere length variation. Biochem. Biophys. Res. Commun. , 291 , 210 –214. · DOI
  46. Wright,W.E. and Shay,J.W. ( 2000 ) Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nature Med. , 6 , 849 –851. · DOI · Paper page
  47. Wright,W.E. and Shay,J.W. ( 2003 ) Telomere shortening and replicative aging. In Hisama,F.M., Weissman,S.M. and Martin,G.M. (eds) Chromosomal Instability and Aging: Basic Science and Clinical Implication . Marcel Dekker, Inc., New York, pp. 51–72. · DOI
  48. Smith,S., Giriat,I., Schmitt,A. and de Lange,T. ( 1998 ) Tankyrase, a poly (ADP-ribose) polymerase at human telomeres. Science , 282 , 1484 –1487. · DOI
  49. Blackburn,E.H. ( 1992 ) Telomerases. Ann. Rev. Biochem. , 61 , 113 –129. · DOI
  50. Bryan,T.M. and Cech,T.R. ( 1999 ) Telomerase and the maintenance of chromosome ends. Curr. Opin. Cell. Biol. , 11 , 318 –324. · DOI · Paper page
  51. Chan,S.W.-L. and Blackburn,E.H. ( 2002 ) New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin. Oncogene , 21 , 553 –563. · DOI
  52. Coursen,J.D., Bennett,W.P., Gollahon,L., Shay,J.W. and Harris,C.C. ( 1997 ) Genomic instability and telomerase activity in human bronchial epithelial cells during immortalization by human papillomavirus-16 E6 and E7 genes. Exp. Cell Res. , 235 , 245 –253. · DOI
  53. Holt,S.E. and Shay,J.W. ( 1999 ) The role of telomerase in cellular proliferation and cancer. J. Cell. Physiol. , 180 , 10 –18. · DOI
  54. Holt,S.E., Wright,W.E. and Shay,J.W. ( 1996 ) Regulation of telomerase activity in immortal cell lines. Mol. Cell. Biol. , 16 , 1932 –1939. · DOI
  55. Jiang,X.R., Jimenez,G., Chang,E. et al . ( 1999 ) Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype. Nature Genet. , 21 , 111 –114. · DOI
  56. Lingner,J., Cooper,J.P. and Cech,T.R. ( 1995 ) Telomerase and DNA end replication: no longer a lagging strand problem? Science , 269 , 1533 –1534. · DOI
  57. Masutomi,K., Yu,E.Y., Khurts,S. et al . ( 2003 ) Telomerase maintains telomere structure in normal human cells. Cell , 114 , 241 –253. · DOI · Paper page
  58. Morales,C.P., Holt,S.E., Ouellette,M., Kaur,K.J., Yan,Y., Wilson,K.S., White,M.A., Wright,W.E. and Shay,J.W. ( 1999 ) Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nature Genet. , 2 , 115 –118. · DOI
  59. Ouellette,M.M., McDaniel,L.D., Wright,W.E., Shay,J.W. and Schultz,R.A. ( 2000 ) The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes. Hum. Mol. Genet. , 9 , 403 –411. · DOI
  60. Ouellette,M.M., Liao,M., Herbert,B.S., Johnson,M., Holt,S.E., Liss,H.S., Shay,J.W. and Wright,W.E. ( 2000 ) Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase. J. Biol. Chem. , 275 , 10072 –10076. · DOI
  61. Shay,J.W. ( 1999 ) Toward identifying a cellular determinant of telomerase repression. J. Natl Cancer Inst. , 91 , 4 –6. · DOI
  62. Shay,J.W. and Wright,W.E. ( 2000 ) The use of telomerized cells for tissue engineering. Nat. Biotechnol.18 , 22 –23. · DOI
  63. Shay,J.W. and Wright,W.E. ( 2002 ) Telomerase: a target for cancer therapeutics. Cancer Cell , 2 , 257 –265. · DOI
  64. Granger,M.P., Wright,W.E. and Shay,J.W. ( 2002 ) Telomerase in cancer and aging. Crit. Rev. Oncol. Hematol. , 41 , 29 –40. · DOI
  65. Steinert,S., Shay,J.W. and Wright,W.E. ( 2000 ) Transient expression of human telomerase extends the life span of normal human fibroblasts. Biochem. Biophys. Res. Commun. , 273 , 1095 –1098. · DOI
  66. Wright,W.E., Piatyszek,M.A., Rainey,W.E., Byrd,W. and Shay,J.W. ( 1996 ) Telomerase activity in human germline and embryonic tissues and cells. Dev. Genet. , 18 , 173 –179. · DOI · Paper page
  67. Wright,W.E., Brasiskyte,D., Piatyszek,M.A. and Shay,J.W. ( 1996 ) Experimental elongation of telomeres in immortal human cells extends the lifespan of immortal×normal cell hybrids. EMBO J. , 15 , 1734 –1741. · DOI
  68. Yang,J., Chang,E., Cherry,A.M., Bangs,C.D., Oei,Y., Bodnar,A., Bronstein,A., Chiu,C.P. and Herron,G.S. ( 1999 ) Human endothelial cell life extension by telomerase expression. J. Biol. Chem. , 274 , 26141 –26148. · DOI · Paper page
  69. Bryan,T.M., Marusic,L., Bacchetti,S., Namba,M. and Reddel,R.R. ( 1997 ) The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit. Hum. Mol. Genet. , 6 , 921 –926. · DOI
  70. Bryan,T.M., Englezou,A., Gupta,J., Bacchetti,S. and Reddel,R.R. ( 1995 ) Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J. , 14 , 4240 –4248. · DOI · Paper page
  71. Dunham,M.A., Neumann,A.A., Fasching,C.L. and Reddel,R.R. ( 2000 ) Telomere maintenance by recombination in human cells. Nature Genet. , 26 , 447 –450. · DOI · Paper page
  72. Reddel,R.R. ( 2003 ) Alternative lengthening of telomeres, telomerase and cancer. Cancer Lett. , 194 , 155 –162. · DOI
  73. Ford,L.P., Zou,Y., Pongracz,K, Gryaznov,S.M., Shay,J.W. and Wright,W.E. ( 2001 ) Telomere maintenance by telomerase can inhibit the ALT pathway in human cells. J. Biol. Chem. , 276 , 32198 –32203. · DOI
  74. Bechter,O.E., Shay,J.W. and Wright,W.E. ( 2004 ) The frequency of homologous recombination in human ALT cells. Cell Cycle , 5 , 49 –51. · DOI
  75. Bechter,O, Zou,Y., Walker,W., Wright,W.E. and Shay,J.W. ( 2004 ) Telomeric recombination in MSH6 deficient human colon cancer cells following telomerase inhibition Cancer Res. , 64 , 3444 –3451. · DOI
  76. Bechter,O.E., Zou,Y., Shay,J.W. and Wright,W.E. ( 2003 ) Homologous recombination in human telomerase positive and ALT cells occurs with the same frequency. EMBO Rep. , 4 , 1138 –1143. · DOI
  77. Aisner,D.L., Wright,W.E. and Shay,J.W. ( 2002 ) Telomerase regulation: not just flipping the switch Curr. Opin. Genet. Dev. , 12 , 80 –85. · DOI
  78. Forsyth,N.R, Wright,W.E. and Shay,J.W. ( 2002 ) Telomerase and differentiation in multicellular organisms: turn it off, turn it on and turn it off again. Differentiation , 69 , 188 –197. · DOI · Paper page
  79. Serrano,M. and Blasco,M. ( 2001 ) Putting the stress on senescence. Curr. Opin. Cell Biol. , 13 , 748 –753. · DOI · Paper page
  80. Drayton,S. and Peters,G. ( 2002 ) Immortalisation and transformation revisited. Curr. Opin. Genet. Dev. , 12 , 98 –104. · DOI
  81. Jones,C.J., Kipling,D., Morris,M. et al . ( 2000 ) Evidence for a telomere-independent ‘clock’ limiting RAS oncogene-driven proliferation of human thyroid epithelial cells. Mol. Cell Biol. , 20 , 5690 –5699. · DOI · Paper page
  82. Dickson,M.A., Hahn,W.C., Ino,Y., Ronfard,V., Wu,J.Y., Weinberg,R.A., Louis,D.N., Li,F.P. and Rheinwald,J.G. ( 2000 ) Human keratinocytes that express hTERT and also bypass a p16 (INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol. Cell. Biol. , 20 , 1436 –1447. · DOI · Paper page
  83. Forsyth,N.R., Evans,A.P., Shay,J.W. and Wright,W.E. ( 2003 ) Developmental differences in the immortalization of lung fibroblasts by telomerase. Aging Cell , 2 , 235 –243. · DOI
  84. Ramirez,R.D., Herbert,B.-S., Vaughn,M.B, Zou,Y., Gandia,K., Morales,C.P., Wright,W.E. and Shay,J.W. ( 2003 ) Bypass of telomere-dependent replicative senescence (M1) upon over expression of CDK4 in normal human epithelial Oncogene , 2 , 433 –444. · DOI
  85. Dimri,G.P., Lee,X., Basile,G. et al . ( 1995 ) A biomarker that identifies senescent human cells in culture and in aging skin in vivo . Proc. Natl Acad. Sci. USA , 92 , 9363 –9367. · DOI · Paper page
  86. Busutil,R.A., Rubio,M., Dolle,M.E.T., Campisi,J. and Vijg,J. ( 2003 ) Oxygen accelerates the accumulation of mutations during senescence and immortalization of murine cells in culture. Aging Cell , 2 , 287 –294. · DOI
  87. Naka,K., Tachibana,A., Ikeda,K. and Motoyama,N. ( 2004 ) Stress-induced premature senescence in hTERT-expressing ataxia telangiectasia fibroblasts. J. Biol. Chem. , 279 , 2030 –2037. · DOI
  88. Baur,J.A., Zou,Y., Shay,J.W. and Wright,W.E. ( 2001 ) Telomere position effect in human cells. Science , 292 , 2075 –2077. · DOI
  89. Koering,C.E., Pollice,A., Zibella,M.P. et al . ( 2002 ) Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep. , 3 , 1055 –1061. · DOI
  90. Shay,J.W. and Wright,W.E. ( 2000 ) Implications of mapping the human telomerase genes (hTERT) as the most distal gene on chromosome 5p. Neoplasia , 2 , 195 –196. · DOI
  91. Zou,Y., Sfeir,A., Shay,J.W. and Wright,W.E. ( 2004 ) Groups of short telomeres determine replicative senescence. Mol. Biol. Cell , 15 , 3709 –3718. · DOI · Paper page
  92. Sedelnikova,O.A., Horikawa,I., Zimonjic,D.B., Popescu,N.C., Bonner,W.M. and Barrett,J.C. ( 2004 ) Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nature Cell Biol. , 6 , 168 –170. · DOI · Paper page
  93. Gire,V., Roux,P., Wynford-Thomas,D., Brondello,J.M. and Dulic,V. ( 2004 ) DNA damage checkpoint kinase Chk2 triggers replicative senescence. EMBO J. , 7 , 2554 –2563. · DOI · Paper page
  94. Takai,H., Smogorzewska,A. and de Lange,T. ( 2003 ) DNA damage foci at dysfunctional telomeres. Curr. Biol. , 13 , 1549 –1556. · DOI · Paper page
  95. Shay,J.W. and Wright,W.E. ( 2004 ) Are telomeres double-strand DNA breaks that are hidden from DNA damage responses? Mol. Cell , 14 , 420 –421. · DOI

Cited by

Metadata

Authors
Shay, J. W., & Wright, W. E.
Venue
Carcinogenesis
Publisher
Oxford University Press (OUP)
Published
2004-10-07
Volume
26
Issue
5
Pages
867-874
ISSN
  • 1460-2180
  • 0143-3334
DOI
10.1093/carcin/bgh296
Cited by
610
References
42
Language
en

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