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How telomeres are replicated

Key Points

  • Telomeres must overcome specific challenges to ensure their efficient replication.

  • In yeast cells, telomeres are replicated in late S phase in agreement with the late firing of subtelomeric origins. By contrast, in humans, subtelomeric origins might be activated earlier, although completion of replication is resumed very late because of delayed replication fork progression at the telomeric DNA repeats.

  • The unusual structures of telomeric chromatin hamper fork progression and may cause fork pause or arrest. We describe the events that allow the cell to alleviate these obstacles, pointing out the role of the telomeric DNA-binding proteins and of DNA-modifying enzymes.

  • Formation of the telomere overhang is a key event in telomere replication and for telomerase recruitment and activity. We describe the different events that lead to telomerase-independent overhang formation. Overhang formation requires fork passage and the leading and the lagging strand may be processed in different ways.

  • The erosion of telomeric DNA can be compensated for by elongation of telomeres by telomerase. We discuss the dynamic binding of telomerase and its associated proteins to telomeres during the cell cycle.


The replication of the ends of linear chromosomes, or telomeres, poses unique problems, which must be solved to maintain genome integrity and to allow cell division to occur. Here, we describe and compare the timing and specific mechanisms that are required to initiate, control and coordinate synthesis of the leading and lagging strands at telomeres in yeasts, ciliates and mammals. Overall, it emerges that telomere replication relies on a strong synergy between the conventional replication machinery, telomere protection systems, DNA-damage-response pathways and chromosomal organization.

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Figure 1: Model for fork progression through chromosome ends in mammalian cells.
Figure 2: Topology and t-loop problems might be coupled during fork progression.
Figure 3: Models for G-tail formation.
Figure 4: Dynamics of telomerase recruitment and activation through the cell cycle in budding yeast.


  1. 1

    McClintock, B. The production of homozygous deficient tissues with mutant characteristics by means of the aberrant mitotic behavior of ring-shaped chromosomes. Genetics 23, 315–376 (1938).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

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

    CAS  PubMed  Google Scholar 

  3. 3

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

    CAS  PubMed  Google Scholar 

  4. 4

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

    CAS  PubMed  Google Scholar 

  5. 5

    Brunori, M., Luciano, P., Gilson, E. & Geli, V. The telomerase cycle: normal and pathological aspects. J. Mol. Med. 83, 244–257 (2005).

    CAS  PubMed  Google Scholar 

  6. 6

    Greider, C. W. & Blackburn, E. H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405–413 (1985).

    CAS  PubMed  Google Scholar 

  7. 7

    Cech, T. R. & Brehm, S. L. Replication of the extrachromosomal ribosomal RNA genes of Tetrahymena thermophilia. Nucleic Acids Res. 9, 3531–3543 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    Wellinger, R. J., Wolf, A. J. & Zakian, V. A. Structural and temporal analysis of telomere replication in yeast. Cold Spring Harb. Symp. Quant. Biol. 58, 725–732 (1993).

    CAS  PubMed  Google Scholar 

  9. 9

    Ivessa, A. S., Zhou, J. Q., Schulz, V. P., Monson, E. K. & Zakian, V. A. Saccharomyces Rrm3p, a 5′ to 3′ DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA. Genes Dev. 16, 1383–1396 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Makovets, S., Herskowitz, I. & Blackburn, E. H. Anatomy and dynamics of DNA replication fork movement in yeast telomeric regions. Mol. Cell. Biol. 24, 4019–4031 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Miller, K. M., Rog, O. & Cooper, J. P. Semi-conservative DNA replication through telomeres requires Taz1. Nature 440, 824–828 (2006). Before this study it was assumed that telomere-binding proteins impede replication fork progression. Conversely, this study shows that Taz1 is crucial for efficient replication fork progression through the telomere.

    CAS  PubMed  Google Scholar 

  12. 12

    Zahler, A. M. & Prescott, D. M. DNA primase and the replication of the telomeres in Oxytricha nova. Nucleic Acids Res. 17, 6299–6317 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Ray, S., Karamysheva, Z., Wang, L., Shippen, D. E. & Price, C. M. Interactions between telomerase and primase physically link the telomere and chromosome replication machinery. Mol. Cell. Biol. 22, 5859–5868 (2002). A physical association of telomerase and primase is shown in Euplotes crassus , supporting the proposed coordinated regulation of telomeric G- and C-strand synthesis.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Dahlen, M., Sunnerhagen, P. & Wang, T. S. Replication proteins influence the maintenance of telomere length and telomerase protein stability. Mol. Cell. Biol. 23, 3031–3042 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Stevenson, J. B. & Gottschling, D. E. Telomeric chromatin modulates replication timing near chromosome ends. Genes Dev. 13, 146–151 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Poloumienko, A., Dershowitz, A., De, J. & Newlon, C. S. Completion of replication map of Saccharomyces cerevisiae chromosome III. Mol. Biol. Cell 12, 3317–3327 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Deng, Z. et al. Telomeric proteins regulate episomal maintenance of Epstein-Barr virus origin of plasmid replication. Mol. Cell 9, 493–503 (2002).

    CAS  PubMed  Google Scholar 

  18. 18

    Amiard, S. et al. A topological mechanism for TRF2-enhanced strand invasion. Nature Struct. Mol. Biol. 14, 147–154 (2007).

    CAS  Google Scholar 

  19. 19

    Verdun, R. E. & Karlseder, J. The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127, 709–720 (2006). Shows that telomere ends need to be recognized as damaged DNA in order for end replication to be completed and for a telomere-specific structure to be formed at chromosome ends after replication.

    CAS  PubMed  Google Scholar 

  20. 20

    Raghuraman, M. K. et al. Replication dynamics of the yeast genome. Science 294, 115–121 (2001).

    CAS  PubMed  Google Scholar 

  21. 21

    Gottschling, D. E., Aparicio, O. M., Billington, B. L. & Zakian, V. A. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63, 751–762 (1990).

    CAS  PubMed  Google Scholar 

  22. 22

    Ferguson, B. M. & Fangman, W. L. A position effect on the time of replication origin activation in yeast. Cell 68, 333–339 (1992).

    CAS  PubMed  Google Scholar 

  23. 23

    Zappulla, D. C., Sternglanz, R. & Leatherwood, J. Control of replication timing by a transcriptional silencer. Curr. Biol. 12, 869–875 (2002).

    CAS  PubMed  Google Scholar 

  24. 24

    Pryde, F. E. & Louis, E. J. Limitations of silencing at native yeast telomeres. EMBO J. 18, 2538–2550 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Wyrick, J. J. et al. Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature 402, 418–421 (1999).

    CAS  PubMed  Google Scholar 

  26. 26

    Cosgrove, A. J., Nieduszynski, C. A. & Donaldson, A. D. Ku complex controls the replication time of DNA in telomere regions. Genes Dev. 16, 2485–2490 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Hiraga, S., Robertson, E. D. & Donaldson, A. D. The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time. EMBO J. 25, 1505–1514 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Raghuraman, M. K., Brewer, B. J. & Fangman, W. L. Cell cycle-dependent establishment of a late replication program. Science 276, 806–809 (1997).

    CAS  PubMed  Google Scholar 

  29. 29

    Wang, Y., Vujcic, M. & Kowalski, D. DNA replication forks pause at silent origins near the HML locus in budding yeast. Mol. Cell. Biol. 21, 4938–4948 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Zou, Y., Gryaznov, S. M., Shay, J. W., Wright, W. E. & Cornforth, M. N. Asynchronous replication timing of telomeres at opposite arms of mammalian chromosomes. Proc. Natl Acad. Sci. USA 101, 12928–12933 (2004).

    CAS  PubMed  Google Scholar 

  31. 31

    Tan, M., Jahn, C. L. & Price, C. M. Origin usage during Euplotes ribosomal DNA amplification. Eukaryot. Cell 2, 115–122 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Wright, W. E., Tesmer, V. M., Liao, M. L. & Shay, J. W. Normal human telomeres are not late replicating. Exp. Cell Res. 251, 492–499 (1999).

    CAS  PubMed  Google Scholar 

  33. 33

    Hultdin, M. et al. Replication timing of human telomeric DNA and other repetitive sequences analyzed by fluorescence in situ hybridization and flow cytometry. Exp. Cell Res. 271, 223–229 (2001).

    CAS  PubMed  Google Scholar 

  34. 34

    Ofir, R., Wong, A. C., McDermid, H. E., Skorecki, K. L. & Selig, S. Position effect of human telomeric repeats on replication timing. Proc. Natl Acad. Sci. USA 96, 11434–11439 (1999).

    CAS  PubMed  Google Scholar 

  35. 35

    Marcand, S., Brevet, V. & Gilson, E. Progressive cis-inhibition of telomerase upon telomere elongation. EMBO J. 18, 3509–3519 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    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). Shows that telomerase does not act on every telomere in each cell cycle and that it exhibits a preference for short telomeres.

    CAS  PubMed  Google Scholar 

  37. 37

    Bianchi, A. & Shore, D. Early replication of short telomeres in budding yeast. Cell 128, 1051–1062 (2007).

    CAS  PubMed  Google Scholar 

  38. 38

    Shirahige, K. et al. Regulation of DNA-replication origins during cell-cycle progression. Nature 395, 618–621 (1998).

    CAS  PubMed  Google Scholar 

  39. 39

    Santocanale, C. & Diffley, J. F. A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature 395, 615–618 (1998).

    CAS  PubMed  Google Scholar 

  40. 40

    Feng, W. et al. Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication. Nature Cell Biol. 8, 148–155 (2006).

    CAS  PubMed  Google Scholar 

  41. 41

    Longhese, M. P., Paciotti, V., Neecke, H. & Lucchini, G. Checkpoint proteins influence telomeric silencing and length maintenance in budding yeast. Genetics 155, 1577–1591 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42

    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). Reports that cells that lack WRN show deletion of telomeres that were replicated by lagging-strand synthesis, suggesting that WRN is necessary for the efficient replication of G-rich telomeric DNA.

    CAS  PubMed  Google Scholar 

  43. 43

    Bai, Y. & Murnane, J. P. Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein. Hum. Genet. 113, 337–347 (2003).

    CAS  PubMed  Google Scholar 

  44. 44

    Shen, J. & Loeb, L. A. Unwinding the molecular basis of the Werner syndrome. Mech. Ageing Dev. 122, 921–944 (2001).

    CAS  PubMed  Google Scholar 

  45. 45

    Du, X. et al. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol. Cell. Biol. 24, 8437–8446 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

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

    CAS  PubMed  Google Scholar 

  47. 47

    Bankhead, T., Kobryn, K. & Chaconas, G. Unexpected twist: harnessing the energy in positive supercoils to control telomere resolution. Mol. Microbiol. 62, 895–905 (2006).

    CAS  PubMed  Google Scholar 

  48. 48

    Ivessa, A. S. & Zakian, V. A. To fire or not to fire: origin activation in Saccharomyces cerevisiae ribosomal DNA. Genes Dev. 16, 2459–2464 (2002).

    CAS  PubMed  Google Scholar 

  49. 49

    Azvolinsky, A., Dunaway, S., Torres, J. Z., Bessler, J. B. & Zakian, V. A. The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes. Genes Dev. 20, 3104–3116 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Schmidt, K. H. & Kolodner, R. D. Suppression of spontaneous genome rearrangements in yeast DNA helicase mutants. Proc. Natl Acad. Sci. USA 103, 18196–18201 (2006).

    CAS  PubMed  Google Scholar 

  51. 51

    Opresko, P. L. et al. The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Mol. Cell 14, 763–74 (2004).

    CAS  PubMed  Google Scholar 

  52. 52

    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).

    CAS  PubMed  Google Scholar 

  53. 53

    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).

    CAS  PubMed  Google Scholar 

  54. 54

    Klobutcher, L. A., Swanton, M. T., Donini, P. & Prescott, D. M. All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3′ terminus. Proc. Natl Acad. Sci. USA 78, 3015–3019 (1981).

    CAS  PubMed  Google Scholar 

  55. 55

    Larrivee, M., LeBel, C. & Wellinger, R. J. The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX complex. Genes Dev. 18, 1391–1396 (2004). Demonstrates that G-tails are present outside S phase on normal yeast telomeres, and that Mre11 is essential to form this constitutive end structure.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    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). Shows that human diploid cells have longer G overhangs at telomeres generated by lagging-strand synthesis than by leading-strand synthesis, which suggests that leading and lagging daughter telomeres are generated differently.

    PubMed  Google Scholar 

  57. 57

    Dionne, I. & Wellinger, R. J. Processing of telomeric DNA ends requires the passage of a replication fork. Nucleic Acids Res. 26, 5365–5371 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Hemann, M. T. & Greider, C. W. G-strand overhangs on telomeres in telomerase-deficient mouse cells. Nucleic Acids Res. 27, 3964–3969 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59

    Ohki, R., Tsurimoto, T. & Ishikawa, F. In vitro reconstitution of the end replication problem. Mol. Cell. Biol. 21, 5753–5766 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Ira, G. et al. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 431, 1011–1017 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Frank, C. J., Hyde, M. & Greider, C. W. Regulation of telomere elongation by the cyclin-dependent kinase CDK1. Mol. Cell 24, 423–432 (2006).

    CAS  PubMed  Google Scholar 

  62. 62

    Vodenicharov, M. D. & Wellinger, R. J. DNA degradation at unprotected telomeres in yeast is regulated by the CDK1 (Cdc28/Clb) cell-cycle kinase. Mol. Cell 24, 127–137 (2006). References 61 and 62 report evidence that cyclin-dependent kinase Cdk1/Cdc28 activity is required for the generation of 3′ single-strand overhangs at telomeres in S. cerevisiae.

    CAS  PubMed  Google Scholar 

  63. 63

    Negrini, S., Ribaud, V., Bianchi, A. & Shore, D. DNA breaks are masked by multiple Rap1 binding in yeast: implications for telomere capping and telomerase regulation. Genes Dev. 21, 292–302 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    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).

    CAS  PubMed  Google Scholar 

  65. 65

    van Overbeek, M. & de Lange, T. Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase. Curr. Biol. 16, 1295–1302 (2006).

    CAS  PubMed  Google Scholar 

  66. 66

    Lenain, C. et al. The Apollo 5′ exonuclease functions together with TRF2 to protect telomeres from DNA repair. Curr. Biol. 16, 1303–1310 (2006).

    CAS  PubMed  Google Scholar 

  67. 67

    Parenteau, J. & Wellinger, R. J. Accumulation of single-stranded DNA and destabilization of telomeric repeats in yeast mutant strains carrying a deletion of RAD27. Mol. Cell. Biol. 19, 4143–4152 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Adams Martin, A., Dionne, I., Wellinger, R. J. & Holm, C. The function of DNA polymerase α at telomeric G tails is important for telomere homeostasis. Mol. Cell. Biol. 20, 786–796 (2000).

    CAS  PubMed  Google Scholar 

  69. 69

    Tomita, K. et al. Fission yeast Dna2 is required for generation of the telomeric single-strand overhang. Mol. Cell. Biol. 24, 9557–9567 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Hubscher, U., Maga, G. & Spadari, S. Eukaryotic DNA polymerases. Annu. Rev. Biochem. 71, 133–163 (2002).

    CAS  PubMed  Google Scholar 

  71. 71

    Qi, H. & Zakian, V. A. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase α and the telomerase-associated est1 protein. Genes Dev. 14, 1777–88 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Carson, M. J. & Hartwell, L. CDC17: an essential gene that prevents telomere elongation in yeast. Cell 42, 249–257 (1985).

    CAS  PubMed  Google Scholar 

  74. 74

    Wellinger, R. J., Wolf, A. J. & Zakian, V. A. Saccharomyces telomeres acquire single-strand TG1–3 tails late in S phase. Cell 72, 51–60 (1993).

    CAS  PubMed  Google Scholar 

  75. 75

    Bertuch, A. A. & Lundblad, V. The Ku heterodimer performs separable activities at double-strand breaks and chromosome termini. Mol. Cell. Biol. 23, 8202–8215 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

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

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77

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

    CAS  PubMed  Google Scholar 

  78. 78

    Zhu, X. D. et al. ERCC1/XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol. Cell 12, 1489–1498 (2003).

    CAS  Google Scholar 

  79. 79

    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).

    CAS  PubMed  Google Scholar 

  80. 80

    Rossi, M. L., Purohit, V., Brandt, P. D. & Bambara, R. A. Lagging strand replication proteins in genome stability and DNA repair. Chem. Rev. 106, 453–473 (2006).

    CAS  PubMed  Google Scholar 

  81. 81

    Budd, M. E., Reis, C. C., Smith, S., Myung, K. & Campbell, J. L. Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase δ. Mol. Cell. Biol. 26, 2490–2500 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Qiu, J., Qian, Y., Frank, P., Wintersberger, U. & Shen, B. Saccharomyces cerevisiae RNase H(35) functions in RNA primer removal during lagging-strand DNA synthesis, most efficiently in cooperation with Rad27 nuclease. Mol. Cell. Biol. 19, 8361–8371 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Jeong, H. S., Backlund, P. S., Chen, H. C., Karavanov, A. A. & Crouch, R. J. RNase H2 of Saccharomyces cerevisiae is a complex of three proteins. Nucleic Acids Res. 32, 407–414 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Reveal, P. M., Henkels, K. M. & Turchi, J. J. Synthesis of the mammalian telomere lagging strand in vitro. J. Biol. Chem. 272, 11678–11681 (1997).

    CAS  PubMed  Google Scholar 

  85. 85

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

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    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).

    CAS  PubMed  Google Scholar 

  87. 87

    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).

    CAS  PubMed  Google Scholar 

  88. 88

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89

    Stansel, R. M., de Lange, T. & Griffith, J. D. T-loop assembly in vitro involves binding of TRF2 near the 3′ telomeric overhang. EMBO J. 20, 5532–5540 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90

    Fouche, N. et al. The basic domain of TRF2 directs binding to DNA junctions irrespective of the presence of TTAGGG repeats. J. Biol. Chem. 281, 37486–37495 (2006).

    CAS  PubMed  Google Scholar 

  91. 91

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

    CAS  PubMed  Google Scholar 

  92. 92

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

    CAS  Google Scholar 

  93. 93

    Gotta, M. et al. The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae. J. Cell Biol. 134, 1349–1363 (1996).

    CAS  PubMed  Google Scholar 

  94. 94

    Heun, P., Laroche, T., Shimada, K., Furrer, P. & Gasser, S. M. Chromosome dynamics in the yeast interphase nucleus. Science 294, 2181–2186 (2001).

    CAS  PubMed  Google Scholar 

  95. 95

    Marcand, S., Brevet, V., Mann, C. & Gilson, E. Cell cycle restriction of telomere elongation. Curr. Biol. 10, 487–490 (2000). Shows that in budding yeast cells that progress synchronously through the cell cycle, telomere elongation coincides with the time of telomere replication.

    CAS  PubMed  Google Scholar 

  96. 96

    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). Shows that the essential DNA polymerase-α and -δ and DNA primase are required for telomerase function, indicating that telomeric DNA synthesis by telomerase is tightly coregulated with the production of the opposite strand.

    CAS  PubMed  Google Scholar 

  97. 97

    Taggart, A. K., Teng, S. C. & Zakian, V. A. Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 297, 1023–1026 (2002). This study correlates the timing of telomere elongation in budding yeast with the binding at the telomeres of several proteins that are involved in telomere elongation, including the telomerase holoenzyme.

    CAS  PubMed  Google Scholar 

  98. 98

    Schramke, V. et al. RPA regulates telomerase action by providing Est1p access to chromosome ends. Nature Genet. 36, 46–54 (2004). Shows that in budding yeast, RPA binds to telomeres at the end of S phase and is required for telomerase action.

    CAS  PubMed  Google Scholar 

  99. 99

    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).

    CAS  PubMed  Google Scholar 

  100. 100

    Osterhage, J. L., Talley, J. M. & Friedman, K. L. Proteasome-dependent degradation of Est1p regulates the cell cycle-restricted assembly of telomerase in Saccharomyces cerevisiae. Nature Struct. Mol. Biol. 13, 720–728 (2006).

    CAS  Google Scholar 

  101. 101

    Goudsouzian, L. K., Tuzon, C. T. & Zakian, V. A. S. cerevisiae Tel1p and Mre11p are required for normal levels of Est1p and Est2p telomere association. Mol. Cell 24, 603–610 (2006).

    CAS  PubMed  Google Scholar 

  102. 102

    Stellwagen, A. E., Haimberger, Z. W., Veatch, J. R. & Gottschling, D. E. Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends. Genes Dev. 17, 2384–2395 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    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).

    CAS  Google Scholar 

  104. 104

    Evans, S. K. & Lundblad, V. Est1 and Cdc13 as comediators of telomerase access. Science 286, 117–120 (1999).

    CAS  PubMed  Google Scholar 

  105. 105

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

    CAS  PubMed  Google Scholar 

  106. 106

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

    CAS  PubMed  Google Scholar 

  107. 107

    Grandin, N., Damon, C. & Charbonneau, M. Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Mol. Cell. Biol. 20, 8397–8408 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. 108

    Seto, A. G., Zaug, A. J., Sobel, S. G., Wolin, S. L. & Cech, T. R. Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature 401, 177–180 (1999).

    CAS  PubMed  Google Scholar 

  109. 109

    Seto, A. G., Livengood, A. J., Tzfati, Y., Blackburn, E. H. & Cech, T. R. A bulged stem tethers Est1p to telomerase RNA in budding yeast. Genes Dev. 16, 2800–2812 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110

    Peterson, S. E. et al. The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku. Nature Genet. 27, 64–67 (2001).

    CAS  PubMed  Google Scholar 

  111. 111

    Dandjinou, A. T. et al. A phylogenetically based secondary structure for the yeast telomerase RNA. Curr. Biol. 14, 1148–1158 (2004).

    CAS  PubMed  Google Scholar 

  112. 112

    Zappulla, D. C. & Cech, T. R. Yeast telomerase RNA: a flexible scaffold for protein subunits. Proc. Natl Acad. Sci. USA 101, 10024–10029 (2004). Based on the interactions of yeast telomerase RNA TLC1 with Est1, Ku and Sm proteins, this study proposes that TLC1 provides a flexible tether for these proteins.

    CAS  PubMed  Google Scholar 

  113. 113

    Zappulla, D. C., Goodrich, K. & Cech, T. R. A miniature yeast telomerase RNA functions in vivo and reconstitutes activity in vitro. Nature Struct. Mol. Biol. 12, 1072–1077 (2005).

    CAS  Google Scholar 

  114. 114

    Gao, H., Cervantes, R. B., Mandell, E. K., Otero, J. H. & Lundblad, V. RPA-like proteins mediate yeast telomere function. Nature Struct. Mol. Biol. 14, 208–214 (2007).

    CAS  Google Scholar 

  115. 115

    Grossi, S., Bianchi, A., Damay, P. & Shore, D. Telomere formation by rap1p binding site arrays reveals end-specific length regulation requirements and active telomeric recombination. Mol. Cell. Biol. 21, 8117–8128 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116

    Boule, J. B., Vega, L. R. & Zakian, V. A. The yeast Pif1p helicase removes telomerase from telomeric DNA. Nature 438, 57–61 (2005). Suggests that Pif1 RNA/DNA helicase activity limits telomerase action by displacing active telomerase from DNA ends.

    CAS  PubMed  Google Scholar 

  117. 117

    Eugster, A. et al. The finger subdomain of yeast telomerase cooperates with Pif1p to limit telomere elongation. Nature Struct. Mol. Biol. 13, 734–739 (2006).

    CAS  Google Scholar 

  118. 118

    Marcand, S., Gilson, E. & Shore, D. A protein-counting mechanism for telomere length regulation in yeast. Science 275, 986–990 (1997).

    CAS  PubMed  Google Scholar 

  119. 119

    Naito, T., Matsuura, A. & Ishikawa, F. Circular chromosome formation in a fission yeast mutant defective in two ATM homologues. Nature Genet. 20, 203–206 (1998).

    CAS  PubMed  Google Scholar 

  120. 120

    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).

    CAS  PubMed  Google Scholar 

  121. 121

    Greenwell, P. W. et al. TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell 82, 823–829 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. 122

    Viscardi, V., Baroni, E., Romano, M., Lucchini, G. & Longhese, M. P. Sudden telomere lengthening triggers a Rad53-dependent checkpoint in Saccharomyces cerevisiae. Mol. Biol. Cell 14, 3126–3143 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124

    Sabourin, M., Tuzon, C.T. & Zakian, V.A. Telomerase and Tel1p preferentially associate with short telomeres in S. cerevisiae. Mol. Cell 27, 550–561 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. 125

    Bianchi, A. & Shore, D. Increased association of telomerase with short telomeres in yeast. Genes Dev. 21, 1726–1730 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. 126

    Hector, R.E. et al. Tel1p preferentially associates with short telomeres to stimulate their elongation. Mol. Cell (in the press).

  127. 127

    Arneriç, M. & Lingner, J. Tel1p kinase and subtelomere bound Tbf1p mediate preferential elongation of short telomeres by telomerase in yeast. EMBO Rep. (in the press).

  128. 128

    Chang, M., Arneric, M., & Lingner, J. Telomerase repeat addition processivity is increased at critically short telomeres in a Tel1-dependent manner in Saccharomyces cerevisiae. Genes Dev. (in the press).

  129. 129

    Berthiau, A. S. et al. Subtelomeric proteins negatively regulate telomere elongation in budding yeast. EMBO J. 25, 846–856 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. 130

    Hediger, F., Berthiau, A. S., van Houwe, G., Gilson, E. & Gasser, S. M. Subtelomeric factors antagonize telomere anchoring and Tel1-independent telomere length regulation. EMBO J. 25, 857–867 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. 131

    Paeschke, K., Simonsson, T., Postberg, J., Rhodes, D. & Lipps, H. J. Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo. Nature Struct. Mol. Biol. 12, 847–854 (2005).

    CAS  Google Scholar 

  132. 132

    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. 279, 13241–13248 (2004).

    CAS  PubMed  Google Scholar 

  133. 133

    Ye, J. Z. et al. POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev. 18, 1649–1654 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. 134

    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).

    CAS  PubMed  Google Scholar 

  135. 135

    Armbruster, B. N. et al. Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1. Mol. Cell. Biol. 24, 3552–3561 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. 136

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

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137

    Lei, M., Zaug, A. J., Podell, E. R. & Cech, T. R. Switching human telomerase on and off with hPOT1 protein in vitro. J. Biol. Chem. 280, 20449–20456 (2005).

    CAS  PubMed  Google Scholar 

  138. 138

    Kim, S. H. et al. TIN2 mediates functions of TRF2 at human telomeres. J. Biol. Chem. 279, 43799–43804 (2004).

    CAS  PubMed  Google Scholar 

  139. 139

    Liu, D. et al. PTOP interacts with POT1 and regulates its localization to telomeres. Nature Cell Biol. 6, 673–680 (2004).

    CAS  PubMed  Google Scholar 

  140. 140

    Ye, J. Z. et al. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J. Biol. Chem. 279, 47264–47271 (2004).

    CAS  PubMed  Google Scholar 

  141. 141

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

    CAS  PubMed  Google Scholar 

  142. 142

    Houghtaling, B. R., Cuttonaro, L., Chang, W. & Smith, S. A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr. Biol. 14, 1621–1631 (2004).

    CAS  PubMed  Google Scholar 

  143. 143

    Murzin, A. G. OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences. EMBO J. 12, 861–867 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144

    Wang, F. et al. The POT1–TPP1 telomere complex is a telomerase processivity factor. Nature 445, 506–510 (2007).

    CAS  PubMed  Google Scholar 

  145. 145

    Xin, H. et al. TPP1 is a homologue of ciliate TEBP-β and interacts with POT1 to recruit telomerase. Nature 445, 559–562 (2007). References 144 and 145 show that the human telomeric proteins TPP1 and POT1 form a complex that regulates telomerase access to the telomere and increases the processivity of the telomerase core enzyme.

    CAS  PubMed  Google Scholar 

  146. 146

    Ancelin, K. 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. 22, 3474–3487 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. 147

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

    CAS  PubMed  Google Scholar 

  148. 148

    Gottschling, D. E. & Cech, T. R. Chromatin structure of the molecular ends of Oxytricha macronuclear DNA: phased nucleosomes and a telomeric complex. Cell 38, 501–510 (1984).

    CAS  PubMed  Google Scholar 

  149. 149

    Wright, J. H., Gottschling, D. E. & Zakian, V. A. Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes Dev. 6, 197–210 (1992).

    CAS  PubMed  Google Scholar 

  150. 150

    Teixeira, M. T. & Gilson, E. Telomere maintenance, function and evolution: the yeast paradigm. Chromosome Res. 13, 535–548 (2005).

    CAS  PubMed  Google Scholar 

  151. 151

    Blasco, M. A. The epigenetic regulation of mammalian telomeres. Nature Rev. Genet. 8, 299–309 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. 152

    Baur, J. A., Zou, Y., Shay, J. W. & Wright, W. E. Telomere position effect in human cells. Science 292, 2075–2077 (2001).

    CAS  PubMed  Google Scholar 

  153. 153

    Koering, C. E. et al. Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep. 3, 1055–1061 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154

    Chong, L. et al. A human telomeric protein. Science 270, 1663–1667 (1995).

    CAS  PubMed  Google Scholar 

  155. 155

    Broccoli, D., Smogorzewska, A., Chong, L. & de Lange, T. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nature Genet. 17, 231–235 (1997).

    CAS  PubMed  Google Scholar 

  156. 156

    Bilaud, T. et al. Telomeric localization of TRF2, a novel human telobox protein. Nature Genet. 17, 236–239 (1997).

    CAS  PubMed  Google Scholar 

  157. 157

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

    CAS  PubMed  Google Scholar 

  158. 158

    Opresko, P. L. et al. POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. J. Biol. Chem. 280, 32069–32080 (2005).

    CAS  PubMed  Google Scholar 

  159. 159

    Zaug, A. J., Podell, E. R. & Cech, T. R. Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro. Proc. Natl Acad. Sci. USA 102, 10864–10869 (2005).

    CAS  PubMed  Google Scholar 

  160. 160

    Griffith, J., Bianchi, A. & de Lange, T. TRF1 promotes parallel pairing of telomeric tracts in vitro. J. Mol. Biol. 278, 79–88 (1998).

    CAS  PubMed  Google Scholar 

  161. 161

    Bae, N. S. & Baumann, P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol. Cell 26, 323–334 (2007).

    CAS  PubMed  Google Scholar 

  162. 162

    Bryan, T. M., Englezou, A., Dalla-Pozza, L., Dunham, M. A. & Reddel, R. R. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nature Med. 3, 1271–1274 (1997).

    CAS  PubMed  Google Scholar 

  163. 163

    Marciniak, R. A. et al. A novel telomere structure in a human alternative lengthening of telomeres cell line. Cancer Res. 65, 2730–2737 (2005).

    CAS  PubMed  Google Scholar 

  164. 164

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

    CAS  PubMed  Google Scholar 

  165. 165

    Biessmann, H. & Mason, J. M. Telomere maintenance without telomerase. Chromosoma 106, 63–69 (1997).

    CAS  PubMed  Google Scholar 

  166. 166

    Pardue, M. L. et al. Two retrotransposons maintain telomeres in Drosophila. Chromosome Res. 13, 443–453 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. 167

    Morrish, T. A. et al. Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres. Nature 446, 208–212 (2007).

    CAS  PubMed  Google Scholar 

  168. 168

    Salas, T. R. et al. Human replication protein A unfolds telomeric G-quadruplexes. Nucleic Acids Res. 34, 4857–4865 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. 169

    Muftuoglu, M. et al. Telomere repeat binding factor 2 interacts with base excision repair proteins and stimulates DNA synthesis by DNA polymerase β. Cancer Res. 66, 113–124 (2006).

    CAS  PubMed  Google Scholar 

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We would like to thank M.-J. Giraud-Panis, T. Teixeira, A. Londono-Vallejo and P. Luciano for critical reading and helpful discussions. The E.G. and V.G. laboratories are supported by 'La Ligue Nationale contre le Cancer' ('Equipes labellisées'). We apologize for all the important papers that could not be cited due to space limitations.

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Cellular senescence

A permanent form of cell-cycle arrest that can be induced by different types of exogenous or endogenous stress. Replicative senescence is triggered by an excessive telomere shortening that is the consequence of multiple rounds of cell division and is considered to be an intrinsic mechanism for limiting the proliferative lifespan of normal somatic cells.

Reverse transcriptase

An enzyme that copies single-stranded RNA into single-stranded DNA.


A multiprotein complex at the junction of the DNA replication fork that contains all the enzymes that are required for DNA replication.


The enzyme that synthesizes an RNA primer for initiation of DNA replication. Primase is associated with DNA polymerase-α to form a four-subunit complex. The polymerase-α–primase complex functions in the initiation of DNA replication at chromosomal origins and in the discontinuous synthesis of Okazaki fragments on the lagging strand of the replication fork.

OB fold

An N-terminal oligonucleotide/oligosaccharide binding (OB) motif. The five-stranded β-sheet forms a closed β-barrel, which is capped by an α-helix located between the third and fourth strands. The OB fold is frequently used for the specific recognition of single-stranded nucleic acids.

Origin recognition complex

A heteromeric six-subunit protein complex that binds to DNA at replication origin sites and functions as a scaffold for the assembly of pre-replicative complexes in the G1 phase of the cell cycle.


The displacement loop structure that results from the displacement of a duplex DNA by a homologous single-stranded DNA.

Position effect

The influence of the chromosomal context on various DNA transactions, including transcription, replication and recombination. It often refers to the repression that is conferred by heterochromatin proximity.

Sir proteins

The silent information regulators (Sir)-2, -3 and -4 are the structural constituents of a particular type of silent chromatin in budding yeast. At telomeres, Sir3 and Sir4 interact with the telomere-binding protein Rap1, can self-associate, and bind to deacetylated and demethylated N-terminal tails of histones H3 and H4 of subtelomeric nucleosomes. The deacetylase activity of Sir2 is required to spread the Sir complex along the chromatin toward the centromere.


A structure adopted by telomeres that may result from invasion of the 3′ overhang into duplex DNA.

G quadruplex

A four-stranded structure that is held together by square planes of four guanines ('G-quartets'), associated through Hoogsteen base pairing. Once such structures form they are extremely stable and are likely to need enzymatic activity to be unwound in vivo.

RecQ helicase

One of a family of evolutionarily conserved helicases, mutations of which can lead to hereditary cancer-predisposition syndromes in humans. Helicases use the energy of ATP hydrolysis to unwind duplex DNA.

DNA topoisomerase

An enzyme that changes DNA supercoiling by inserting or removing superhelical twists.

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Gilson, E., Géli, V. How telomeres are replicated. Nat Rev Mol Cell Biol 8, 825–838 (2007).

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