Skip to main content

Telomere-Binding Proteins in Humans

  • Chapter

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Shelterin, the telomere-secific protein complex, is essential for genome stability and cell viability. Shelterin accumulates at telomeres and transforms chromosome ends into specialized structures that evade recognition by the DNA damage signaling and repair machineries and are maintained through consecutive cell divisions. Shelterin accomplishes these tasks through its ability to remodel the telomeric DNA into a protected structure and to locally inhibit the activation of the DNA damage response. Furthermore, shelterin plays an essential role in controlling telomere length homeostasis by suppressing excessive nuclease activity at the chromosome terminus and by regulating telomerase. The capacities of the telomere-binding proteins to prevent genome instability and to influence telomere length make shelterin an essential factor in both normal cell growth and tumorigenesis.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Mcclintock B, The stability of broken ends of chromosomes in zea mays. Genetics 1941; 26:234–82.

    CAS  PubMed  Google Scholar 

  2. Moyzis RK, Buckingham J, Cram L et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA 1988; 85:6622–26.

    CAS  PubMed  Google Scholar 

  3. Makarov VL, Hirose Y, Langmore JP. Long g tails at both ends of human chromosomes suggest a c strand degradation mechanism for telomere shortening. Cell 1997; 88:657–66.

    CAS  PubMed  Google Scholar 

  4. Zhong Z, Shiue L, Kaplan S, De Lange T. A mammalian factor that binds telomeric ttaggg repeats in vitro. Mol Cell Biol 1992; 12:4834–43.

    CAS  PubMed  Google Scholar 

  5. De Lange T. Shelterin: The protein complex that shapes and safeguards human telomeres. Genes Dev 2005; 19:2100–10.

    PubMed  Google Scholar 

  6. Harley CB. Telomere loss: Mitotic clock or genetic time bomb? Mutat Res 1991; 256:271–82.

    CAS  PubMed  Google Scholar 

  7. Watson JD. Origin of concatemeric t7 DNA. Nat New Biol 1972; 239:197–201.

    CAS  PubMed  Google Scholar 

  8. Olovnikov AM. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 1973; 41:181–90.

    CAS  PubMed  Google Scholar 

  9. Hemann MT, Greider CW. G-strand overhangs on telomeres in telomerase-deficient mouse cells. Nucleic Acids Res 1999; 27:3964–69.

    CAS  PubMed  Google Scholar 

  10. Huffman KE, Levene SD, Tesmer VM, Shay JW, Wright WE. Telomere shortening is proportional to the size of the g-rich telomeric 3′-overhang. J Biol Chem 2000; 275:19719–22.

    CAS  PubMed  Google Scholar 

  11. Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. J Mol Biol 1992; 225:951–60.

    CAS  PubMed  Google Scholar 

  12. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345:458–60.

    CAS  PubMed  Google Scholar 

  13. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37:614–36.

    CAS  PubMed  Google Scholar 

  14. Bodnar AG, Ouellette M, Frolkis M et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279:349–52.

    CAS  PubMed  Google Scholar 

  15. Morales CP, Holt SE, Ouellette M et al. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nat Genet 1999; 21:115–18.

    CAS  PubMed  Google Scholar 

  16. Kim NW, Piatyszek MA, Prowse KR et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266:2011–15.

    CAS  PubMed  Google Scholar 

  17. Shay JW, Pereira-Smith OM, Wright WE. A role for both rb and p53 in the regulation of human cellular senescence. Exp Cell Res 1991; 196:33–39.

    CAS  PubMed  Google Scholar 

  18. Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E. Telomeric localization of trf2, a novel human telobox protein. Nat Genet 1997; 17:236–39.

    CAS  PubMed  Google Scholar 

  19. Broccoli D, Smogorzewska A, Chong L, De Lange T. Human telomeres contain two distinct myb-related proteins, trf1 and trf2. Nat Genet 1997; 17:231–35.

    CAS  PubMed  Google Scholar 

  20. Bianchi A, Stansel RM, Fairall L, Griffith JD, Rhodes D, De Lange T. Trf1 binds a bipartite telomeric site with extreme spatial flexibility. Embo J 1999; 18:5735–44.

    CAS  PubMed  Google Scholar 

  21. Court R, Chapman L, Fairall L, Rhodes D. How the human telomeric proteins trf1 and trf2 recognize telomeric DNA: A view from high-resolution crystal structures. EMBO Rep 2005; 6:39–45.

    CAS  PubMed  Google Scholar 

  22. Hanaoka S, Nagadoi A, Nishimura Y. Comparison between trf2 and trf1 of their telomeric DNA-bound structures and DNA-binding activities. Protein Sci 2005; 14:119–30.

    CAS  PubMed  Google Scholar 

  23. Bianchi A, Smith S, Chong L, Elias P, De Lange T. Trf1 is a dimer and bends telomeric DNA. Embo J 1997; 16:1785–94.

    CAS  PubMed  Google Scholar 

  24. Griffith J, Bianchi A, De Lange T. Trf1 promotes parallel pairing of telomeric tracts in vitro. J Mol Biol 1998; 278:79–88.

    CAS  PubMed  Google Scholar 

  25. Karlseder J, Kachatrian L, Takai H et al. Targeted deletion reveals an essential function for the telomere length regulator trf1. Mol Cell Biol 2003; 23:6533–41.

    CAS  PubMed  Google Scholar 

  26. Iwano T, Tachibana M, Reth M, Shinkai Y. Importance of trf1 for functional telomere structure. J Biol Chem 2004; 279:1442–48.

    CAS  PubMed  Google Scholar 

  27. Celli G, De Lange T. DNA processing not required for atm-mediated telomere damage response after trf2 deletion. Nat Cell Biol 2005; 7:712–18.

    CAS  PubMed  Google Scholar 

  28. Kim SH, Kaminker P, Campisi J. Tin2, a new regulator of telomere length in human cells. Nat Genet 1999; 23:405–12.

    CAS  PubMed  Google Scholar 

  29. Ye JZ, Donigian JR, Van Overbeek M et al. Tin2 binds trf1 and trf2 simultaneously and stabilizes the trf2 complex on telomeres. J Biol Chem 2004; 279:47264–71.

    CAS  PubMed  Google Scholar 

  30. Ye JZ, Hockemeyer D, Krutchinsky AN et al. Pot1-interacting protein pip1: A telomere length regulator that recruits pot1 to the tin2/trf1 complex. Genes Dev 2004; 18:1649–54.

    CAS  PubMed  Google Scholar 

  31. Kim SH, Beausejour C, Davalos AR, Kaminker P, Heo SJ, Campisi J. Tin2 mediates functions of trf2 at human telomeres. J Biol Chem 2004; 279:43799–804.

    CAS  PubMed  Google Scholar 

  32. Houghtaling BR, Cuttonaro L, Chang W, Smith S. A dynamic molecular link between the telomere length regulator trf1 and the chromosome end protector trf2. Curr Biol 2004; 14:1621–31.

    CAS  PubMed  Google Scholar 

  33. Smith S, Giriat I, Schmitt A, De Lange T. Tankyrase, a poly(adp-ribose) polymerase at human telomeres. Science 1998; 282:1484–87.

    CAS  PubMed  Google Scholar 

  34. Ye JZ, De Lange T. Tin2 is a tankyrase 1 parp modulator in the trf1 telomere length control complex. Nat Genet 2004; 36:618–23.

    CAS  PubMed  Google Scholar 

  35. Liu D, Safari A, O'connor MS et al. Ptop interacts with pot1 and regulates its localization to telomeres. Nat Cell Biol 2004; 6:673–80.

    CAS  PubMed  Google Scholar 

  36. Baumann P, Cech TR. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 2001; 292:1171–75.

    CAS  PubMed  Google Scholar 

  37. Loayza D, De Lange T. Pot1 as a terminal transducer of trf1 telomere length control. Nature 2003; 424:1013–18.

    Google Scholar 

  38. Lei M, Podell ER, Cech TR. Structure of human pot1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol 2004; 11:1223–29.

    CAS  PubMed  Google Scholar 

  39. Loayza D, Parsons H, Donigian J, Hoke K, De Lange T. DNA binding features of human pot1: A nonamer 5′ -tagggttag-3′ minimal binding site, sequence specificity, and internal binding to multimeric sites. J Biol Chem 2004; 279:13241–48.

    CAS  PubMed  Google Scholar 

  40. Hockemeyer D, Palm W, Else T et al. Telomere protection by mammalian pot1 requires interaction with tpp1. Nat Struct Mol Biol 2007; 14:754–61.

    CAS  PubMed  Google Scholar 

  41. Xin H, Liu D, Wan M et al. Tpp1 is a homologue of ciliate tebp-beta and interacts with pot1 to recruit telomerase. Nature 2007; 445:559–62.

    CAS  PubMed  Google Scholar 

  42. Hockemeyer D, Sfeir A, Shay J, Wright WE, De Lange T. Pot1 protects telomeres from a transient DNA damage response and determines how human chromosomes end. EMBO J. 2005; 24:2667–78.

    CAS  PubMed  Google Scholar 

  43. Hockemeyer D, Daniels J, Takai H, De Lange T. Recent expansion of the telomeric complex in rodents: Two distinct pot1 proteins protect mouse telomeres. Cell 2006; 126:63–77.

    CAS  PubMed  Google Scholar 

  44. Wu L, Multani A, He H et al. Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 2006; 126:49–62.

    CAS  PubMed  Google Scholar 

  45. Li B, Oestreich S, De Lange T. Identification of human rap1: Implications for telomere evolution. Cell 2000; 101:471–83.

    CAS  PubMed  Google Scholar 

  46. Zhu XD, Kuster B, Mann M, Petrini JH, De Lange T. Cell-cycle-regulated association of rad50/mre11/nbs1 with trf2 and human telomeres. Nat Genet 2000; 25:347–52.

    CAS  PubMed  Google Scholar 

  47. Zhu XD, Niedernhofer L, Kuster B, Mann M, Hoeijmakers JH, De Lange T. Ercc1/xpf removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol Cell 2003; 12:1489–98.

    CAS  PubMed  Google Scholar 

  48. Van Overbeek M, De Lange T. Apollo, an artemis-related nuclease, interacts with trf2 and protects human telomeres in s phase. Curr Biol 2006; 16:1295–302.

    PubMed  Google Scholar 

  49. Lenain C, Bauwens S, Amiard S, Brunori M, Giraud-Panis MJ, Gilson E. The apollo 5′ exonuclease functions together with trf2 to protect telomeres from DNA repair. Curr Biol 2006; 16:1303–10.

    CAS  PubMed  Google Scholar 

  50. Hsu HL, Gilley D, Blackburn EH, Chen DJ. Ku is associated with the telomere in mammals. Proc Natl Acad Sci USA 1999; 96:12454–58.

    CAS  PubMed  Google Scholar 

  51. D'adda Di Fagagna F, Hande MP, Tong WM et al. Effects of DNA nonhomologous end joining factors on telomere length and chromosomal stability in mammalian cells. Curr Biol 2001; 11:1192–96.

    PubMed  Google Scholar 

  52. O'connor MS, Safari A, Liu D, Qin J, Songyang Z. The human rap1 protein complex and modulation of telomere length. J Biol Chem 2004; 279:28585–91.

    PubMed  Google Scholar 

  53. Song K, Jung D, Jung Y, Lee SG, Lee I. Interaction of human ku70 with trf2. FEBS Lett 2000; 481:81–85.

    CAS  PubMed  Google Scholar 

  54. Crabbe L, Verdun RE, Haggblom CI, Karlseder J. Defective telomere lagging strandynthesis in cells lacking wrn helicase activity. Science 2004; 306:1951–53.

    CAS  PubMed  Google Scholar 

  55. Lillard-Wetherell K, Machwe A, Langland GT et al. Association and regulation of the blm helicase by the telomere proteins trf1 and trf2. Hum Mol Genet 2004; 13:1919–32.

    CAS  PubMed  Google Scholar 

  56. Machwe A, Xiao L, Orren DK. Trf2 recruits the werner syndrome (wrn) exonuclease for processing of telomeric DNA. Oncogene 2004; 23:149–56.

    CAS  PubMed  Google Scholar 

  57. Opresko PL, Von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA. Telomere binding protein trf2 binds to and stimulates the werner and bloom syndrome helicases. J Biol Chem 2002; 277:41110–19.

    CAS  PubMed  Google Scholar 

  58. Tarsounas M, Munoz P, Claas A et al. Telomere maintenance requires the rad51d recombination/repair protein. Cell 2004; 117:337–47.

    CAS  PubMed  Google Scholar 

  59. Bailey SM, Meyne J, Chen DJ et al. DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes. Proc Natl Acad Sci USA 1999; 96:14899–904.

    CAS  PubMed  Google Scholar 

  60. Ozgenc A, Loeb LA. Current advances in unraveling the function of the werner syndrome protein. Mutat Res 2005; 577:237–51.

    CAS  PubMed  Google Scholar 

  61. Wright WE, Tesmer VM, Huffman K, Levene SD, Shay JW. Normal human chromosomes have long g-rich telomeric overhangs at one end. Genes Dev 1997; 11:2801–09.

    CAS  PubMed  Google Scholar 

  62. Sfeir A, Chai W, Shay JW, Wright WE. Telomere-end processing the terminal nucleotides of human chromosomes. Mol Cell 2005; 18:131–38.

    CAS  PubMed  Google Scholar 

  63. Hockemeyer D, Palm W, Wang RC, Couto SS, De Lange T. Engineered telomere degradation models dyskeratosis congenita. Genes Dev 2008; 22:1773–85.

    CAS  PubMed  Google Scholar 

  64. De Lange T. T-loops and the origin of telomeres. Nature Rev Mol Cell Biol 2004; 5:323–29.

    Google Scholar 

  65. Griffith JD, Comeau L, Rosenfield S et al. Mammalian telomeres end in a large duplex loop. Cell 1999; 97:503–14.

    CAS  PubMed  Google Scholar 

  66. Nikitina T, Woodcock CL. Closed chromatin loops at the ends of chromosomes. J Cell Biol 2004; 166:161–65.

    CAS  PubMed  Google Scholar 

  67. Stansel RM, De Lange T, Griffith J. T-loop assembly in vitro involves binding of trf2 near the 3′ telomeric overhang. EMBO J 2001; 20:5532–40.

    CAS  PubMed  Google Scholar 

  68. Amiard S, Doudeau M, Pinte S et al. A topological mechanism for trf2-enhanced strand invasion. Nat Struct Mol Biol 2007; 14:147–54.

    CAS  PubMed  Google Scholar 

  69. Haber J. Telomeres thrown for a loop. Mol Cell 2004; 16:502–03.

    CAS  PubMed  Google Scholar 

  70. Bucholc M, Park Y, Lustig AJ. Intrachromatid excision of telomeric DNA as a mechanism for telomere size control in saccharomyces cerevisiae. Mol Cell Biol 2001; 21:6559–73.

    CAS  PubMed  Google Scholar 

  71. Wang RC, Smogorzewska A, De Lange T. Homologous recombination generates t-loop-sized deletions at human telomeres. Cell 2004; 119:355–68.

    CAS  PubMed  Google Scholar 

  72. Fouche N, Cesare AJ, Willcox S, Ozgur S, Compton S, Griffith J. The basic domain of trf2 directs binding to DNA junctions irrespective of the presence of ttaggg repeats. J Biol Chem 2006; 281:37486–95.

    CAS  PubMed  Google Scholar 

  73. Cesare AJ, Griffith JD. Telomeric DNA in alt cells is characterized by free telomeric circles and heterogeneous t-loops. Mol Cell Biol 2004; 24:9948–57.

    CAS  PubMed  Google Scholar 

  74. Reddel RR. Alternative lengthening of telomeres, telomerase, and cancer. Cancer Lett 2003; 194:155–62.

    CAS  PubMed  Google Scholar 

  75. Zou L, Elledge SJ. Sensing DNA damage through atrip recognition of rpa-ssdna complexes. Science 2003; 300:1542–48.

    CAS  PubMed  Google Scholar 

  76. Liu Q, Guntuku S, Cui XS et al. Chk1 is an essential kinase that is regulated by atr and required for the g(2)/m DNA damage checkpoint. Genes Dev 2000; 14:1448–59.

    CAS  PubMed  Google Scholar 

  77. Lazzerini Denchi E, De Lange T. Protection of telomeres through independent control of atm and atr by trf2 and pot1. Nature 2007; 448:1068–71.

    Google Scholar 

  78. Chaturvedi P, Eng WK, Zhu Y et al. Mammalian chk2 is a downstream effector of the atm dependent DNA damage checkpoint pathway. Oncogene 1999; 18:4047–54.

    CAS  PubMed  Google Scholar 

  79. Van Steensel B, Smogorzewska A, De Lange T. Trf2 protects human telomeres from end-to-end fusions. Cell 1998; 92:401–13.

    PubMed  Google Scholar 

  80. Takai H, Smogorzewska A, De Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol 2003; 13:1549–56.

    CAS  PubMed  Google Scholar 

  81. Karlseder J, Broccoli D, Dai Y, Hardy S, De Lange T. P53- and atm-dependent apoptosis induced by telomeres lacking trf2. Science 1999; 283:1321–25.

    CAS  PubMed  Google Scholar 

  82. Smogorzewska A, De Lange T. Different telomere damage signaling pathways in human and mouse cells. Embo J 2002; 21:4338–48.

    CAS  PubMed  Google Scholar 

  83. Smogorzewska A, Karlseder J, Holtgreve-Grez H, Jauch A, De Lange T. DNA ligase iv-dependent nhej of deprotected mammalian telomeres in g1 and g2. Curr Biol 2002; 12:1635.

    CAS  PubMed  Google Scholar 

  84. Celli G, Lazzerini Denchi E, De Lange T. Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat Cell Biol 2006; 8: 885–90.

    PubMed  Google Scholar 

  85. Karlseder J, Hoke K, Mirzoeva OK et al. The telomeric protein trf2 binds the atm kinase and can inhibit the atm-dependent DNA damage response. PLoS Biol 2004; 2:E240.

    PubMed  Google Scholar 

  86. McClintock B, in The fusion of broken ends of sister half-chromatids following chromatid breakage at meiotic anaphase, Ed. (Garland Publishing, Inc, New York and London, 1938), pp. 1–48.

    Google Scholar 

  87. Dimitrova N, De Lange T. Mdc1 accelerates nonhomologous end-joining of dysfunctional telomeres. Genes Dev 2006; 20:3238–43.

    CAS  PubMed  Google Scholar 

  88. Bae N, Baumann P. A rap1/trf2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol Cell 2007; 26:323–34.

    CAS  PubMed  Google Scholar 

  89. Capper R, Britt-Compton B, Tankimanova M et al. The nature of telomere fusion and a definition of the critical telomere length in human cells. Genes Dev 2007; 21:2495–508.

    CAS  PubMed  Google Scholar 

  90. Smogorzewska A, De Lange T. Regulation of telomerase by telomeric proteins. Ann Rev Biochem 2004; 73:177–208.

    CAS  PubMed  Google Scholar 

  91. Van Steensel B, De Lange T. Control of telomere length by the human telomeric protein trf1. Nature 1997; 385:740–43.

    PubMed  Google Scholar 

  92. Smogorzewska A, Van Steensel B, Bianchi A et al. Control of human telomere length by trf1 and trf2. Mol Cell Biol 2000; 20:1659–68.

    CAS  PubMed  Google Scholar 

  93. Ancelin K, Brunori M, Bauwens S et al. Targeting assay to study the cis functions of human telomeric proteins: Evidence for inhibition of telomerase by trf1 and for activation of telomere degradation by trf2. Mol Cell Biol 2002; 22:3474–87.

    CAS  PubMed  Google Scholar 

  94. Marcand S, Gilson E, Shore D. A protein-counting mechanism for telomere length regulation in yeast. Science 1997; 275:986–90.

    CAS  PubMed  Google Scholar 

  95. Kelleher C, Kurth I, Lingner J. Human protection of telomeres 1 (pot1) is a negative regulator of telomerase activity in vitro. Mol Cell Biol 2005; 25:808–18.

    CAS  PubMed  Google Scholar 

  96. Lei M, Zaug AJ, Podell ER, Cech TR. Switching human telomerase on and off with hpot1 protein in vitro. J Biol Chem 2005; 280:20449–56.

    CAS  PubMed  Google Scholar 

  97. Wang F, Podell E, Zaug AJ et al. The pot1-tpp1 telomere complex is a telomerase processivity factor. Nature 2007; 445:506–10.

    CAS  PubMed  Google Scholar 

  98. Karlseder J, Smogorzewska A, De Lange T. Senescence induced by altered telomere state, not telomere loss. Science 2002; 295:2446–49.

    CAS  PubMed  Google Scholar 

  99. Li B, De Lange T. Rap1 affects the length and heterogeneity of human telomeres. Mol Biol Cell 2003; 14:5060–68.

    CAS  PubMed  Google Scholar 

  100. Smith S, De Lange T. Tankyrase promotes telomere elongation in human cells. Curr Biol 2000; 10:1299–302.

    CAS  PubMed  Google Scholar 

  101. Seimiya H, Muramatsu Y, Smith S, Tsuruo T. Functional subdomain in the ankyrin domain of tankyrase 1 required for poly(adp-ribosyl)ation of trf1 and telomere elongation. Mol Cell Biol 2004; 24:1944–55.

    CAS  PubMed  Google Scholar 

  102. Donigian J, De Lange T. The role of the poly(adp-ribose) polymerase tankyrase1 in telomere length control by the trf1 component of the shelterin complex. J Biol Chem 2007; 282:22662–67.

    CAS  PubMed  Google Scholar 

  103. Dynek JN, Smith S. Resolution of sister telomere association is required for progression through mitosis. Science 2004; 304:97–100.

    CAS  PubMed  Google Scholar 

  104. Cohen S, Me G, Lovrecz G, Bache N, Robinson P, Reddel RR. Protein composition of catalytically active human telomerase from immortal cells. Science 2007; 315:1850–53.

    CAS  PubMed  Google Scholar 

  105. Cristofari G, Lingner J. Telomere length homeostasis requires that telomerase levels are limiting. EMBO J 2006; 25:565–74.

    CAS  PubMed  Google Scholar 

  106. Bakkenist CJ, Drissi R, Wu J, Kastan MB, Dome JS. Disappearance of the telomere dysfunction-induced stress response in fully senescent cells. Cancer Res 2004; 64:3748–52.

    CAS  PubMed  Google Scholar 

  107. D'adda Di Fagagna F, Reaper PM, Clay-Farrace L et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003; 426:194–98.

    PubMed  Google Scholar 

  108. Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM. Telomere shortening triggers senescence of human cells through a pathway involving atm, p53, and p21(cip1), but not p16(ink4a). Mol Cell 2004; 14:501–13.

    CAS  PubMed  Google Scholar 

  109. Artandi SE, Depinho RA. A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr Opin Genet Dev 2000; 10:39–46.

    CAS  PubMed  Google Scholar 

  110. Campisi J. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol 2001; 11:S27–31.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science + Business Media, LLC

About this chapter

Cite this chapter

Dimitrova, N. (2009). Telomere-Binding Proteins in Humans. In: Hiyama, K. (eds) Telomeres and Telomerase in Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-879-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-879-9_2

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-306-0

  • Online ISBN: 978-1-60327-879-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics