Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Replication and protection of telomeres

Abstract

During the evolution of linear genomes, it became essential to protect the natural chromosome ends to prevent triggering of the DNA-damage repair machinery and enzymatic attack. Telomeres — tightly regulated complexes consisting of repetitive G-rich DNA and specialized proteins — accomplish this task. Telomeres not only conceal linear chromosome ends from detection and inappropriate repair but also provide a buffer to counteract replication-associated shortening. Lessons from many model organisms have taught us about the complications of maintaining these specialized structures. Here, we discuss how telomeres interact and cooperate with the DNA replication and DNA-damage repair machineries.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: The mammalian telomeric complex.
Figure 2: Telomere shortening, senescence and cancer.
Figure 3: End replication and processing.

References

  1. Griffith, J. D. et al. Mammalian telomeres end in a large duplex loop. Cell 97, 503–514 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. de Lange, T. T-loops and the origin of telomeres. Nature Rev. Mol. Cell Biol. 5, 323–329 (2004).

    Article  CAS  Google Scholar 

  3. Gottschling, D. E. & Zakian, V. A. Telomere proteins: specific recognition and protection of the natural termini of Oxytricha macronuclear DNA. Cell 47, 195–205 (1986).

    Article  CAS  PubMed  Google Scholar 

  4. Price, C. M. & Cech, T. R. Telomeric DNA–protein interactions of Oxytricha macronuclear DNA. Genes Dev. 1, 783–793 (1987).

    Article  CAS  PubMed  Google Scholar 

  5. Gray, J. T., Celander, D. W., Price, C. M. & Cech, T. R. Cloning and expression of genes for the Oxytricha telomere-binding protein: specific subunit interactions in the telomeric complex. Cell 67, 807–814 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. Horvath, M. P., Schweiker, V. L., Bevilacqua, J. M., Ruggles, J. A. & Schultz, S. C. Crystal structure of the Oxytricha nova telomere end binding protein complexed with single strand DNA. Cell 95, 963–974 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. van Steensel, B. & de Lange, T. Control of telomere length by the human telomeric protein TRF1. Nature 385, 740–743 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. van Steensel, B., Smogorzewska, A. & de Lange, T. TRF2 protects human telomeres from end-to-end fusions. Cell 92, 401–413 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Smogorzewska, A. et al. Control of human telomere length by TRF1 and TRF2. Mol. Cell. Biol. 20, 1659–1668 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Karlseder, J. et al. Targeted deletion reveals an essential function for the telomere length regulator Trf1. Mol. Cell. Biol. 23, 6533–6541 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Watson, J. D. Origin of concatemeric T7 DNA. Nature New Biol. 239, 197–201 (1972).

    Article  CAS  PubMed  Google Scholar 

  13. Olovnikov, A. M. A theory of marginotomy. J. Theor. Biol. 41, 181–190 (1973).

    Article  CAS  PubMed  Google Scholar 

  14. Hayflick, L. & Moorhead, P. S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621 (1961).

    Article  CAS  PubMed  Google Scholar 

  15. Lundblad, V. & Szostak, J. W. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57, 633–643 (1989).

    Article  CAS  PubMed  Google Scholar 

  16. Bodnar, A. G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349–352 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Singer, M. S. & Gottschling, D. E. TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science 266, 404–409 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Lendvay, T. S., Morris, D. K., Sah, J., Balasubramanian, B. & Lundblad, V. Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics 144, 1399–1412 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lingner, J. et al. Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276, 561–567 (1997).

    Article  CAS  PubMed  Google Scholar 

  20. Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Counter, C. M. et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 11, 1921–1929 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shay, J. W. & Wright, W. E. Hayflick, his limit, and cellular ageing. Nature Rev. Mol. Cell Biol. 1, 72–76 (2000).

    Article  CAS  Google Scholar 

  23. de Lange, T. Protection of mammalian telomeres. Oncogene 21, 532–540 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Sandell, L. L. & Zakian, V. A. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 75, 729–739 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. Smogorzewska, A. & de Lange, T. Different telomere damage signaling pathways in human and mouse cells. EMBO J. 21, 4338–4348 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Karlseder, J., Smogorzewska, A. & de Lange, T. Senescence induced by altered telomere state, not telomere loss. Science 295, 2446–2449 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Takai, H., Smogorzewska, A. & de Lange, T. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13, 1549–1556 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. d'Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. de Lange, T. & Jacks, T. For better or worse? Telomerase inhibition and cancer. Cell 98, 273–275 (1999).

    Article  CAS  PubMed  Google Scholar 

  30. Seger, Y. R. et al. Transformation of normal human cells in the absence of telomerase activation. Cancer Cell 2, 401–413 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Artandi, S. E. & DePinho, R. A. A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr. Opin. Genet. Dev. 10, 39–46 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Reddel, R. R. & Bryan, T. M. Alternative lengthening of telomeres: dangerous road less travelled. Lancet 361, 1840–1841 (2003).

    Article  PubMed  Google Scholar 

  33. Dunham, M. A., Neumann, A. A., Fasching, C. L. & Reddel, R. R. Telomere maintenance by recombination in human cells. Nature Genet. 26, 447–450 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Varley, H., Pickett, H. A., Foxon, J. L., Reddel, R. R. & Royle, N. J. Molecular characterization of inter-telomere and intra-telomere mutations in human ALT cells. Nature Genet. 30, 301–305 (2002).

    Article  PubMed  Google Scholar 

  35. Morales, C. P. et al. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nature Genet. 21, 115–118 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

  36. Cooke, H. J. & Smith, B. A. Variability at the telomeres of the human X/Y pseudoautosomal region. Cold Spring Harb. Symp. Quant. Biol. 51, 213–219 (1986).

    Article  CAS  PubMed  Google Scholar 

  37. Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J. M. Cellular senescence in aging primates. Science 311, 1257 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Joeng, K. S., Song, E. J., Lee, K. J. & Lee, J. Long lifespan in worms with long telomeric DNA. Nature Genet. 36, 607–611 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Raices, M., Maruyama, H., Dillin, A. & Karlseder, J. Uncoupling of longevity and telomere length in C. elegans. PLoS Genet. 1, e30 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Teixeira, M. T., Arneric, M., Sperisen, P. & Lingner, J. Telomere length homeostasis is achieved via a switch between telomerase-extendible and -nonextendible states. Cell 117, 323–335 (2004).

    Article  CAS  PubMed  Google Scholar 

  41. Cristofari, G. & Lingner, J. Telomere length homeostasis requires that telomerase levels are limiting. EMBO J. 25, 565–574 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Blasco, M. A. et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34 (1997).

    Article  CAS  PubMed  Google Scholar 

  43. Lee, H. W. et al. Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  44. Liu, Y. et al. The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo. Curr. Biol. 10, 1459–1462 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Fan, X. & Price, C. M. Coordinate regulation of G- and C strand length during new telomere synthesis. Mol. Biol. Cell 8, 2145–2155 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Diede, S. J. & Gottschling, D. E. Telomerase-mediated telomere addition in vivo requires DNA primase and DNA polymerases α and δ. Cell 99, 723–733 (1999).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  48. Bianchi, A., Negrini, S. & Shore, D. Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdc13 and Est1. Mol. Cell 16, 139–146 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Chandra, A., Hughes, T. R., Nugent, C. I. & Lundblad, V. Cdc13 both positively and negatively regulates telomere replication. Genes Dev. 15, 404–414 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Grossi, S., Puglisi, A., Dmitriev, P. V., Lopes, M. & Shore, D. Pol12, the B subunit of DNA polymerase α, functions in both telomere capping and length regulation. Genes Dev. 18, 992–1006 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Nakamura, M., Nabetani, A., Mizuno, T., Hanaoka, F. & Ishikawa, F. Alterations of DNA and chromatin structures at telomeres and genetic instability in mouse cells defective in DNA polymerase α. Mol. Cell. Biol. 25, 11073–11088 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rhodes, D. & Giraldo, R. Telomere structure and function. Curr. Opin. Struct. Biol. 5, 311–322 (1995).

    Article  CAS  PubMed  Google Scholar 

  53. Miller, K. M., Rog, O. & Cooper, J. P. Semi-conservative DNA replication through telomeres requires Taz1. Nature 440, 824–828 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  55. Chang, S. et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nature Genet. 36, 877–882 (2004).

    Article  CAS  PubMed  Google Scholar 

  56. Jacob, N. K., Skopp, R. & Price, C. M. G-overhang dynamics at Tetrahymena telomeres. EMBO J. 20, 4299–4308 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wellinger, R. J., Ethier, K., Labrecque, P. & Zakian, V. A. Evidence for a new step in telomere maintenance. Cell 85, 423–433 (1996).

    Article  CAS  PubMed  Google Scholar 

  58. Dionne, I. & Wellinger, R. J. Cell cycle-regulated generation of single-stranded G-rich DNA in the absence of telomerase. Proc. Natl Acad. Sci. USA 93, 13902–13907 (1996).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  59. Makarov, V. L., Hirose, Y. & Langmore, J. P. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 88, 657–666 (1997).

    Article  CAS  PubMed  Google Scholar 

  60. Chai, W., Du, Q., Shay, J. W. & Wright, W. E. Human telomeres have different overhang sizes at leading versus lagging strands. Mol. Cell 21, 427–435 (2006).

    Article  PubMed  CAS  Google Scholar 

  61. Jacob, N. K., Kirk, K. E. & Price, C. M. Generation of telomeric G strand overhangs involves both G and C strand cleavage. Mol. Cell 11, 1021–1032 (2003).

    Article  CAS  PubMed  Google Scholar 

  62. Sfeir, A. J., Chai, W., Shay, J. W. & Wright, W. E. Telomere-end processing the terminal nucleotides of human chromosomes. Mol. Cell 18, 131–138 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ferreira, M. G. & Cooper, J. P. The fission yeast Taz1 protein protects chromosomes from Ku-dependent end-to-end fusions. Mol. Cell 7, 55–63 (2001).

    Article  CAS  PubMed  Google Scholar 

  65. Mieczkowski, P. A., Mieczkowska, J. O., Dominska, M. & Petes, T. D. Genetic regulation of telomere–telomere fusions in the yeast Saccharomyces cerevisae. Proc. Natl Acad. Sci. USA 100, 10854–10859 (2003).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  66. 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. 12, 1635 (2002).

    Article  CAS  PubMed  Google Scholar 

  67. Fisher, T. S., Taggart, A. K. & Zakian, V. A. Cell cycle-dependent regulation of yeast telomerase by Ku. Nature Struct. Mol. Biol. 11, 1198–1205 (2004).

    Article  CAS  Google Scholar 

  68. Fisher, T. S. & Zakian, V. A. Ku: a multifunctional protein involved in telomere maintenance. DNA Repair (Amst.) 4, 1215–1226 (2005).

    Article  CAS  Google Scholar 

  69. Lin, J. J. & Zakian, V. A. The Saccharomyces CDC13 protein is a single-strand TG1–3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo. Proc. Natl Acad. Sci. USA 93, 13760–13765 (1996).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  70. Grandin, N., Reed, S. I. & Charbonneau, M. Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes Dev. 11, 512–527 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Grandin, N., Damon, C. & Charbonneau, M. Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13. EMBO J. 20, 1173–1183 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Garvik, B., Carson, M. & Hartwell, L. Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol. Cell. Biol. 15, 6128–6138 (1995); erratum 16, 457 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Booth, C., Griffith, E., Brady, G. & Lydall, D. Quantitative amplification of single-stranded DNA (QAOS) demonstrates that cdc13-1 mutants generate ssDNA in a telomere to centromere direction. Nucleic Acids Res. 29, 4414–4422 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cooper, J. P., Nimmo, E. R., Allshire, R. C. & Cech, T. R. Regulation of telomere length and function by a Myb-domain protein in fission yeast. Nature 385, 744–747 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  75. Baumann, P. & Cech, T. R. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292, 1171–1175 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  76. Loayza, D. & de Lange, T. POT1 as a terminal transducer of TRF1 telomere length control. Nature 423, 1013–1018 (2003).

    Article  ADS  CAS  PubMed  Google Scholar 

  77. Colgin, L. M., Baran, K., Baumann, P., Cech, T. R. & Reddel, R. R. Human POT1 facilitates telomere elongation by telomerase. Curr. Biol. 13, 942–946 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. Hockemeyer, D., Daniels, J. P., Takai, H. & de Lange, T. Recent expansion of the telomeric complex in rodents: two distinct POT1 proteins protect mouse telomeres. Cell 126, 63–77 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Wu, L. et al. Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell 126, 49–62 (2006).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  81. Wang, R. C., Smogorzewska, A. & de Lange, T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119, 355–368 (2004).

    Article  CAS  PubMed  Google Scholar 

  82. Nugent, C. I. et al. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr. Biol. 8, 657–660 (1998).

    Article  CAS  PubMed  Google Scholar 

  83. Tsukamoto, Y., Taggart, A. K. & Zakian, V. A. The role of the Mre11–Rad50–Xrs2 complex in telomerase-mediated lengthening of Saccharomyces cerevisiae telomeres. Curr. Biol. 11, 1328–1335 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Takata, H., Tanaka, Y. & Matsuura, A. Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae. Mol. Cell 17, 573–583 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Nakamura, T. M., Moser, B. A. & Russell, P. Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres. Genetics 161, 1437–1452 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Takata, H., Kanoh, Y., Gunge, N., Shirahige, K. & Matsuura, A. Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo. Mol. Cell 14, 515–522 (2004).

    Article  CAS  PubMed  Google Scholar 

  87. Chan, S. W., Chang, J., Prescott, J. & Blackburn, E. H. Altering telomere structure allows telomerase to act in yeast lacking ATM kinases. Curr. Biol. 11, 1240–1250 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Chan, S. W. & Blackburn, E. H. Telomerase and ATM/Tel1p protect telomeres from nonhomologous end joining. Mol. Cell 11, 1379–1387 (2003).

    Article  CAS  PubMed  Google Scholar 

  89. Vaziri, H. et al. ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J. 16, 6018–6033 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ranganathan, V. et al. Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit. Curr. Biol. 11, 962–966 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Zhu, X. D., Kuster, B., Mann, M., Petrini, J. H. & de Lange, T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nature Genet. 25, 347–352 (2000).

    Article  CAS  PubMed  Google Scholar 

  92. Verdun, R. E., Crabbe, L., Haggblom, C. & Karlseder, J. Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol. Cell 20, 551–561 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. Verdun, R. E. & Karlseder, J. The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127, 709–720 (2006).

    Article  CAS  PubMed  Google Scholar 

  94. Cesare, A. J. & Griffith, J. D. Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol. Cell. Biol. 24, 9948–9957 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bailey, S. M., Brenneman, M. A. & Goodwin, E. H. Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res. 32, 3743–3751 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Bechter, O. E., Shay, J. W. & Wright, W. E. The frequency of homologous recombination in human ALT cells. Cell Cycle 3, 547–549 (2004).

    Article  CAS  PubMed  Google Scholar 

  97. McEachern, M. J. & Haber, J. E. Break-induced replication and recombinational telomere elongation in yeast. Annu. Rev. Biochem. 75, 111–135 (2006).

    Article  CAS  PubMed  Google Scholar 

  98. Lundblad, V. Telomere maintenance without telomerase. Oncogene 21, 522–531 (2002).

    Article  CAS  PubMed  Google Scholar 

  99. Carson, C. T. et al. The Mre11 complex is required for ATM activation and the G2/M checkpoint. EMBO J. 22, 6610–6620 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Haber, J. E. Partners and pathways repairing a double-strand break. Trends Genet. 16, 259–264 (2000).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to V. Lundblad for constructive comments on the manuscript, the National Institutes of Health for funding (J.K.) and the Leukemia and Lymphoma Society for a long-term postdoctoral fellowship (R.E.V.).

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Verdun, R., Karlseder, J. Replication and protection of telomeres. Nature 447, 924–931 (2007). https://doi.org/10.1038/nature05976

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05976

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing