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Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization

Lim, Ci Ji, Cech, Thomas R.·2021·Nature Reviews Molecular Cell Biology
DOI 10.1038/s41580-021-00328-yPMC PMC8221230
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  1. Moyzis, R. K. et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl Acad. Sci. USA 85, 6622–6626 (1988). · DOI
  2. Meyne, J., Ratliff, R. L. & Moyzis, R. K. Conservation of the human telomere sequence (TTAGGG)n among vertebrates. Proc. Natl Acad. Sci. USA 86, 7049–7053 (1989). · DOI
  3. 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). · DOI
  4. Lansdorp, P. M. et al. Heterogeneity in telomere length of human chromosomes. Hum. Mol. Genet. 5, 685–691 (1996). · DOI
  5. Vaziri, H. et al. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52, 661–667 (1993).
  6. Allsopp, R. C. et al. Telomere length predicts replicative capacity of human fibroblasts. Proc. Natl Acad. Sci. USA 89, 10114–10118 (1992). · DOI · Paper page
  7. Mitchell, J. R., Wood, E. & Collins, K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402, 551–555 (1999). · DOI · Paper page
  8. Vulliamy, T. J., Knight, S. W., Mason, P. J. & Dokal, I. Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita. Blood Cell Mol. Dis. 27, 353–357 (2001). · DOI
  9. 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). · DOI
  10. Liu, D., O’Connor, M. S., Qin, J. & Songyang, Z. Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J. Biol. Chem. 279, 51338–51342 (2004). · DOI · Paper page
  11. 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). Together with Liu et al. (J. Biol. Chem. 2004), this study identifies the full six-member shelterin complex, showing TIN2 binding both TRF1 and TRF2. · DOI
  12. Baumann, P. & Cech, T. R. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292, 1171–1175 (2001). · DOI · Paper page
  13. Lei, M., Podell, E. R. & Cech, T. R. Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat. Struct. Mol. Biol. 11, 1223–1229 (2004). · DOI
  14. Griffith, J. D. et al. Mammalian telomeres end in a large duplex loop. Cell 97, 503–514 (1999). This study reports that a substantial fraction of mammalian telomeres form a dsDNA loop to protect chromosome ends. · DOI · Paper page
  15. 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). · DOI
  16. Nikitina, T. & Woodcock, C. L. Closed chromatin loops at the ends of chromosomes. J. Cell Biol. 166, 161–165 (2004). · DOI
  17. Li, J. S. et al. TZAP: a telomere-associated protein involved in telomere length control. Science 355, 638–641 (2017). This study reports a telomeric DNA-binding protein that initiates trimming of long telomeres. · DOI
  18. Lingner, J. et al. Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276, 561–567 (1997). This study and Greider and Blackburn (1989) report the first cloning of genes for the RNA and the catalytic (TERT) subunits of telomerase in ciliated protozoa, which led to the identification of the corresponding human factors. · DOI · Paper page
  19. Greider, C. W. Telomerase is processive. Mol. Cell Biol. 11, 4572–4580 (1991).
  20. Roake, C. M. & Artandi, S. E. Regulation of human telomerase in homeostasis and disease. Nat. Rev. Mol. Cell Biol. 21, 384–397 (2020). · DOI
  21. Schmidt, J. C. & Cech, T. R. Human telomerase: biogenesis, trafficking, recruitment, and activation. Genes Dev. 29, 1095–1105 (2015). · DOI
  22. Hockemeyer, D. & Collins, K. Control of telomerase action at human telomeres. Nat. Struct. Mol. Biol. 22, 848–852 (2015). · DOI
  23. Wright, W. E., Piatyszek, M. A., Rainey, W. E., Byrd, W. & Shay, J. W. Telomerase activity in human germline and embryonic tissues and cells. Dev. Genet. 18, 173–179 (1996). · DOI · Paper page
  24. Nandakumar, J. et al. The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature 492, 285–289 (2012). · DOI
  25. Zhong, F. L. et al. TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to chromosome ends. Cell 150, 481–494 (2012). · DOI
  26. Sexton, A. N., Youmans, D. T. & Collins, K. Specificity requirements for human telomere protein interaction with telomerase holoenzyme. J. Biol. Chem. 287, 34455–34464 (2012). Together with Nandakumar et. al. (2012) and Zhong et. al. (2012), this study identifies specific amino acids of the TPP1 OB fold that recruit telomerase and enhance its enzymatic processivity. · DOI
  27. Chen, L. Y., Redon, S. & Lingner, J. The human CST complex is a terminator of telomerase activity. Nature 488, 540–544 (2012). · DOI
  28. Gao, H., Cervantes, R. B., Mandell, E. K., Otero, J. H. & Lundblad, V. RPA-like proteins mediate yeast telomere function. Nat. Struct. Mol. Biol. 14, 208–214 (2007). · DOI
  29. Miyake, Y. et al. RPA-like mammalian Ctc1–Stn1–Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol. Cell 36, 193–206 (2009). · DOI · Paper page
  30. Surovtseva, Y. V. et al. Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Mol. Cell 36, 207–218 (2009). Together with Miyake et al. (2009), this study shows that the RPA-like CST complex, previously characterized in yeast telomeres, has mammalian and plant counterparts with telomeric functions. · DOI
  31. Casteel, D. E. et al. A DNA polymerase-α primase cofactor with homology to replication protein A-32 regulates DNA replication in mammalian cells. J. Biol. Chem. 284, 5807–5818 (2009). · DOI
  32. Azzalin, C. M., Reichenbach, P., Khoriauli, L., Giulotto, E. & Lingner, J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318, 798–801 (2007). · DOI
  33. Kim, S. H., Kaminker, P. & Campisi, J. TIN2, a new regulator of telomere length in human cells. Nat. Genet. 23, 405–412 (1999). · DOI · Paper page
  34. Li, B. & de Lange, T. Rap1 affects the length and heterogeneity of human telomeres. Mol. Biol. Cell 14, 5060–5068 (2003). · DOI
  35. 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). · DOI
  36. Bilaud, T. et al. Telomeric localization of TRF2, a novel human telobox protein. Nat. Genet. 17, 236–239 (1997). · DOI
  37. Loayza, D. & De Lange, T. POT1 as a terminal transducer of TRF1 telomere length control. Nature 423, 1013–1018 (2003). · DOI
  38. Lim, C., Zaug, A. J., Kim, H. J. & Cech, T. R. Reconstitution of human shelterin complexes reveals unexpected stoichiometry and dual pathways to enhance telomerase processivity. Nat. Commun. 8, 1075 (2017).
  39. Rai, R., Chen, Y., Lei, M. & Chang, S. TRF2–RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions. Nat. Commun. 7, 10881 (2016).
  40. Sfeir, A., Kabir, S., van Overbeek, M., Celli, G. B. & de Lange, T. Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. Science 327, 1657–1661 (2010). · DOI
  41. Lototska, L. et al. Human RAP1 specifically protects telomeres of senescent cells from DNA damage. EMBO Rep. 21, e49076 (2020). · DOI
  42. Xin, H. et al. TPP1 is a homologue of ciliate TEBP-β and interacts with POT1 to recruit telomerase. Nature 445, 559–562 (2007). · DOI
  43. 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). · DOI
  44. Rice, C. et al. Structural and functional analysis of the human POT1–TPP1 telomeric complex. Nat. Commun. 8, 14928 (2017).
  45. Chen, C. et al. Structural insights into POT1–TPP1 interaction and POT1 C-terminal mutations in human cancer. Nat. Commun. 8, 14929 (2017).
  46. Kar, A., Willcox, S. & Griffith, J. D. Transcription of telomeric DNA leads to high levels of homologous recombination and T-loops. Nucleic Acids Res. 44, 9369–9380 (2016).
  47. Hu, C. et al. Structural and functional analyses of the mammalian TIN2–TPP1–TRF2 telomeric complex. Cell Res. 27, 1485–1502 (2017). This study reports the crystal structure of the key ‘bridge’ region of mammalian shelterin, which connects its dsDNA-binding and ssDNA-binding subunits. · DOI
  48. Chen, L. Y. et al. Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control. Mol. Cell 47, 839–850 (2012). · DOI
  49. Chen, Y. et al. A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science 319, 1092–1096 (2008). · DOI
  50. Fairall, L., Chapman, L., Moss, H., de Lange, T. & Rhodes, D. Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2. Mol. Cell 8, 351–361 (2001). · DOI
  51. Bianchi, A. et al. TRF1 binds a bipartite telomeric site with extreme spatial flexibility. EMBO J. 18, 5735–5744 (1999). · DOI · Paper page
  52. Nishikawa, T., Nagadoi, A., Yoshimura, S., Aimoto, S. & Nishimura, Y. Solution structure of the DNA-binding domain of human telomeric protein, hTRF1. Structure 6, 1057–1065 (1998). · DOI
  53. 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. 6, 39–45 (2005). · DOI
  54. Smith, S. & de Lange, T. TRF1, a mammalian telomeric protein. Trends Genet. 13, 21–26 (1997). · DOI
  55. 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. 24, 1944–1955 (2004). · DOI
  56. Poulet, A. et al. The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA. Nucleic Acids Res. 40, 2566–2576 (2012). · DOI
  57. Saint-Leger, A. et al. The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres. Cell Cycle 13, 2469–2474 (2014). · DOI
  58. Necasova, I., Janouskova, E., Klumpler, T. & Hofr, C. Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it. Nucleic Acids Res. 45, 12599 (2017). · DOI
  59. Schmutz, I., Timashev, L., Xie, W., Patel, D. J. & de Lange, T. TRF2 binds branched DNA to safeguard telomere integrity. Nat. Struct. Mol. Biol. 24, 734–742 (2017). · DOI
  60. Konishi, A., Izumi, T. & Shimizu, S. TRF2 protein interacts with core histones to stabilize chromosome ends. J. Biol. Chem. 291, 20798–20810 (2016). · DOI
  61. Wang, R. C., Smogorzewska, A. & de Lange, T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119, 355–368 (2004). · DOI
  62. 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). · DOI
  63. Williamson, J. R., Raghuraman, M. K. & Cech, T. R. Monovalent cation-induced structure of telomeric DNA: the G-quartet model. Cell 59, 871–880 (1989). · DOI
  64. Sundquist, W. I. & Klug, A. Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops. Nature 342, 825–829 (1989). · DOI
  65. Pedroso, I. M., Hayward, W. & Fletcher, T. M. The effect of the TRF2 N-terminal and TRFH regions on telomeric G-quadruplex structures. Nucleic Acids Res. 37, 1541–1554 (2009). · DOI
  66. Janouskova, E. et al. Human Rap1 modulates TRF2 attraction to telomeric DNA. Nucleic Acids Res. 43, 2691–2700 (2015). · DOI
  67. Choi, K. H., Farrell, A. S., Lakamp, A. S. & Ouellette, M. M. Characterization of the DNA binding specificity of Shelterin complexes. Nucleic Acids Res. 39, 9206–9223 (2011). · DOI
  68. Erdel, F. et al. Telomere recognition and assembly mechanism of mammalian shelterin. Cell Rep. 18, 41–53 (2017). · DOI
  69. Hanaoka, S., Nagadoi, A. & Nishimura, Y. Comparison between TRF2 and TRF1 of their telomeric DNA-bound structures and DNA-binding activities. Protein Sci. 14, 119–130 (2005). · DOI
  70. Nishikawa, T. et al. Structure of the DNA-binding domain of human telomeric protein, TRF1 and its interaction with telomeric DNA. Nucleic Acids Res. Suppl. 1, 273–274 (2001). · DOI
  71. Takai, K. K., Hooper, S., Blackwood, S., Gandhi, R. & de Lange, T. In vivo stoichiometry of shelterin components. J. Biol. Chem. 285, 1457–1467 (2010). · DOI
  72. Pike, A. M., Strong, M. A., Ouyang, J. P. T. & Greider, C. W. TIN2 functions with TPP1/POT1 to stimulate telomerase processivity. Mol. Cell Biol. 39, e00593-18 (2019).
  73. Nelson, N. D. et al. The C-terminal extension unique to the long isoform of the shelterin component TIN2 enhances its interaction with TRF2 in a phosphorylation- and dyskeratosis congenita cluster-dependent fashion. Mol. Cell Biol. 38, e00025-18 (2018). · DOI
  74. Grill, S. et al. Two separation-of-function isoforms of human TPP1 dictate telomerase regulation in somatic and germ cells. Cell Rep. 27, 3511–3521.e7 (2019). · DOI
  75. Zemp, I. & Lingner, J. The shelterin component TPP1 is a binding partner and substrate for the deubiquitinating enzyme USP7. J. Biol. Chem. 289, 28595–28606 (2014). · DOI
  76. Bhanot, M. & Smith, S. TIN2 stability is regulated by the E3 ligase Siah2. Mol. Cell Biol. 32, 376–384 (2012). · DOI
  77. Janovic, T., Stojaspal, M., Veverka, P., Horakova, D. & Hofr, C. Human telomere repeat binding factor TRF1 replaces TRF2 bound to shelterin core hub TIN2 when TPP1 is absent. J. Mol. Biol. 431, 3289–3301 (2019). · DOI
  78. Kim, J. K. et al. Structural basis for shelterin bridge assembly. Mol. Cell 68, 698–714.e5 (2017). · DOI
  79. Zhang, Y. et al. Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment. Proc. Natl Acad. Sci. USA 110, 5457–5462 (2013). · DOI
  80. 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). · DOI
  81. Yang, Q., Zheng, Y. L. & Harris, C. C. POT1 and TRF2 cooperate to maintain telomeric integrity. Mol. Cell Biol. 25, 1070–1080 (2005). · DOI
  82. Timashev, L. A. & de Lange, T. Characterization of T-loop formation by TRF2. Nucleus 11, 164–177 (2020). · DOI
  83. Amiard, S. et al. A topological mechanism for TRF2-enhanced strand invasion. Nat. Struct. Mol. Biol. 14, 147–154 (2007). · DOI
  84. Subramaniam, S. The cryo-EM revolution: fueling the next phase. IUCrJ 6, 1–2 (2019). · DOI
  85. Cheng, Y. Single-particle cryo-EM — how did it get here and where will it go. Science 361, 876–880 (2018). · DOI
  86. Jiang, J. et al. Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions. Science 350, aab4070 (2015). · DOI
  87. Nguyen, T. H. D. et al. Cryo-EM structure of substrate-bound human telomerase holoenzyme. Nature 557, 190–195 (2018). · DOI
  88. Schmidt, J. C., Zaug, A. J. & Cech, T. R. Live cell imaging reveals the dynamics of telomerase recruitment to telomeres. Cell 166, 1188–1197.e9 (2016). · DOI
  89. Schmidt, J. C., Zaug, A. J., Kufer, R. & Cech, T. R. Dynamics of human telomerase recruitment depend on template-telomere base pairing. Mol. Biol. Cell 29, 869–880 (2018). · DOI
  90. Laprade, H. et al. Single-molecule imaging of telomerase RNA reveals a recruitment-retention model for telomere elongation. Mol. Cell 79, 115–126.e6 (2020). · DOI
  91. Lin, J. et al. TRF1 and TRF2 use different mechanisms to find telomeric DNA but share a novel mechanism to search for protein partners at telomeres. Nucleic Acids Res. 42, 2493–2504 (2014). · DOI
  92. Denchi, E. L. & de Lange, T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 448, 1068–1071 (2007). This study establishes roles of shelterin components in subduing specific signalling pathways that detect DNA damage but need to be repressed at natural chromosome ends. · DOI · Paper page
  93. Flynn, R. L. et al. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471, 532–536 (2011). · DOI
  94. Wang, H., Nora, G. J., Ghodke, H. & Opresko, P. L. Single molecule studies of physiologically relevant telomeric tails reveal POT1 mechanism for promoting G-quadruplex unfolding. J. Biol. Chem. 286, 7479–7489 (2011). · DOI
  95. 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). · DOI
  96. Zahler, A. M., Williamson, J. R., Cech, T. R. & Prescott, D. M. Inhibition of telomerase by G-quartet DNA structures. Nature 350, 718–720 (1991). · DOI
  97. Hwang, H., Buncher, N., Opresko, P. L. & Myong, S. POT1–TPP1 regulates telomeric overhang structural dynamics. Structure 20, 1872–1880 (2012). · DOI
  98. Jansson, L. I. et al. Telomere DNA G-quadruplex folding within actively extending human telomerase. Proc. Natl Acad. Sci. USA 116, 9350–9359 (2019). · DOI
  99. Patrick, E. M., Slivka, J. D., Payne, B., Comstock, M. J. & Schmidt, J. C. Observation of processive telomerase catalysis using high-resolution optical tweezers. Nat. Chem. Biol. 16, 801–809 (2020). · DOI
  100. Latrick, C. M. & Cech, T. R. POT1–TPP1 enhances telomerase processivity by slowing primer dissociation and aiding translocation. EMBO J. 29, 924–933 (2010). · DOI
  101. Paudel, B. P. et al. A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution. eLife 9, e56428 (2020). · DOI
  102. Wang, F. et al. Human CST has independent functions during telomere duplex replication and C-strand fill-in. Cell Rep. 2, 1096–1103 (2012). · DOI
  103. Huang, C., Dai, X. & Chai, W. Human Stn1 protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in. Cell Res. 22, 1681–1695 (2012). · DOI
  104. Wang, Y., Brady, K. S., Caiello, B. P., Ackerson, S. M. & Stewart, J. A. Human CST suppresses origin licensing and promotes AND-1/Ctf4 chromatin association. Life Sci. Alliance 2, e201800270 (2019).
  105. Stewart, J. A. et al. Human CST promotes telomere duplex replication and general replication restart after fork stalling. EMBO J. 31, 3537–3549 (2012). · DOI
  106. Zhang, M. et al. Mammalian CST averts replication failure by preventing G-quadruplex accumulation. Nucleic Acids Res. 47, 5243–5259 (2019). · DOI
  107. Wang, F., Stewart, J. & Price, C. M. Human CST abundance determines recovery from diverse forms of DNA damage and replication stress. Cell Cycle 13, 3488–3498 (2014). · DOI
  108. Barazas, M. et al. The CST complex mediates end protection at double-strand breaks and promotes PARP inhibitor sensitivity in BRCA1-deficient cells. Cell Rep. 23, 2107–2118 (2018). · DOI
  109. Mirman, Z. et al. 53BP1-RIF1-shieldin counteracts DSB resection through CST- and Polα-dependent fill-in. Nature 560, 112–116 (2018). · DOI
  110. Bochkareva, E., Korolev, S., Lees-Miller, S. P. & Bochkarev, A. Structure of the RPA trimerization core and its role in the multistep DNA-binding mechanism of RPA. EMBO J. 21, 1855–1863 (2002). · DOI
  111. Bochkareva, E., Belegu, V., Korolev, S. & Bochkarev, A. Structure of the major single-stranded DNA-binding domain of replication protein A suggests a dynamic mechanism for DNA binding. EMBO J. 20, 612–618 (2001). · DOI
  112. Shastrula, P. K., Rice, C. T., Wang, Z., Lieberman, P. M. & Skordalakes, E. Structural and functional analysis of an OB-fold in human Ctc1 implicated in telomere maintenance and bone marrow syndromes. Nucleic Acids Res. 46, 972–984 (2018). · DOI
  113. Bryan, C., Rice, C., Harkisheimer, M., Schultz, D. C. & Skordalakes, E. Structure of the human telomeric Stn1–Ten1 capping complex. PLoS ONE 8, e66756 (2013).
  114. Bhattacharjee, A., Wang, Y., Diao, J. & Price, C. M. Dynamic DNA binding, junction recognition and G4 melting activity underlie the telomeric and genome-wide roles of human CST. Nucleic Acids Res. 45, 12311–12324 (2017). · DOI
  115. Hom, R. A. & Wuttke, D. S. Human CST prefers G-rich but not necessarily telomeric sequences. Biochemistry 56, 4210–4218 (2017). · DOI
  116. Chen, L. Y., Majerska, J. & Lingner, J. Molecular basis of telomere syndrome caused by CTC1 mutations. Genes Dev. 27, 2099–2108 (2013). · DOI
  117. Gu, P. et al. CTC1–STN1 coordinates G- and C-strand synthesis to regulate telomere length. Aging Cell 17, e12783 (2018).
  118. Feng, X. et al. CTC1–STN1 terminates telomerase while STN1–TEN1 enables C-strand synthesis during telomere replication in colon cancer cells. Nat. Commun. 9, 2827 (2018).
  119. Fan, J. & Pavletich, N. P. Structure and conformational change of a replication protein A heterotrimer bound to ssDNA. Genes Dev. 26, 2337–2347 (2012). · DOI
  120. Gao, Y. et al. Structures and operating principles of the replisome. Science 363, eaav7003 (2019). · DOI
  121. Ge, Y. et al. Structural insights into telomere protection and homeostasis regulation by yeast CST complex. Nat. Struct. Mol. Biol. 27, 752–762 (2020). · DOI
  122. Wan, B. et al. The Tetrahymena telomerase p75–p45–p19 subcomplex is a unique CST complex. Nat. Struct. Mol. Biol. 22, 1023–1026 (2015). · DOI
  123. Lue, N. F. et al. The telomere capping complex CST has an unusual stoichiometry, makes multipartite interaction with G-tails, and unfolds higher-order G-tail structures. PLoS Genet. 9, e1003145 (2013).
  124. Gelinas, A. D. et al. Telomere capping proteins are structurally related to RPA with an additional telomere-specific domain. Proc. Natl Acad. Sci. USA 106, 19298–19303 (2009). · DOI
  125. Sun, J. et al. Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase α. Cell Res. 21, 258–274 (2011). · DOI
  126. Rice, C. & Skordalakes, E. Structure and function of the telomeric CST complex. Comput. Struct. Biotechnol. J. 14, 161–167 (2016). · DOI
  127. Zeng, Z. et al. Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. Proc. Natl Acad. Sci. USA 108, 20357–20361 (2011). · DOI
  128. Goulian, M., Heard, C. J. & Grimm, S. L. Purification and properties of an accessory protein for DNA polymerase α/primase. J. Biol. Chem. 265, 13221–13230 (1990). · DOI
  129. Zhao, Y. et al. Telomere extension occurs at most chromosome ends and is uncoupled from fill-in in human cancer cells. Cell 138, 463–475 (2009). · DOI
  130. Kratz, K. & de Lange, T. Protection of telomeres 1 proteins POT1a and POT1b can repress ATR signaling by RPA exclusion, but binding to CST limits ATR repression by POT1b. J. Biol. Chem. 293, 14384–14392 (2018). · DOI
  131. Wan, M., Qin, J., Songyang, Z. & Liu, D. OB fold-containing protein 1 (OBFC1), a human homolog of yeast Stn1, associates with TPP1 and is implicated in telomere length regulation. J. Biol. Chem. 284, 26725–26731 (2009). · DOI
  132. Tesmer, V. M., Smith, E. M., Danciu, O., Padmanaban, S. & Nandakumar, J. Combining conservation and species-specific differences to determine how human telomerase binds telomeres. Proc. Natl Acad. Sci. USA 116, 26505–26515 (2019). · DOI
  133. Wu, P., Takai, H. & de Lange, T. Telomeric 3′ overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST. Cell 150, 39–52 (2012). · DOI
  134. Feng, X., Hsu, S. J., Kasbek, C., Chaiken, M. & Price, C. M. CTC1-mediated C-strand fill-in is an essential step in telomere length maintenance. Nucleic Acids Res. 45, 4281–4293 (2017). · DOI
  135. Diotti, R., Kalan, S., Matveyenko, A. & Loayza, D. DNA-directed polymerase subunits play a vital role in human telomeric overhang processing. Mol. Cancer Res. 13, 402–410 (2015). · DOI
  136. Porcella, S. Y. et al. Separable, Ctf4-mediated recruitment of DNA polymerase α for initiation of DNA synthesis at replication origins and lagging-strand priming during replication elongation. PLoS Genet. 16, e1008755 (2020). · DOI
  137. Kilkenny, M. L. et al. The human CTF4-orthologue AND-1 interacts with DNA polymerase α/primase via its unique C-terminal HMG box. Open. Biol. 7, 170217 (2017). · DOI
  138. Nakaoka, H., Nishiyama, A., Saito, M. & Ishikawa, F. Xenopus laevis Ctc1–Stn1–Ten1 (xCST) protein complex is involved in priming DNA synthesis on single-stranded DNA template in Xenopus egg extract. J. Biol. Chem. 287, 619–627 (2012). · DOI
  139. Ganduri, S. & Lue, N. F. STN1–POLA2 interaction provides a basis for primase-pol α stimulation by human STN1. Nucleic Acids Res. 45, 9455–9466 (2017). · DOI
  140. Nunez-Ramirez, R. et al. Flexible tethering of primase and DNA pol α in the eukaryotic primosome. Nucleic Acids Res. 39, 8187–8199 (2011). · DOI
  141. Leteurtre, F. et al. Accelerated telomere shortening and telomerase activation in Fanconi’s anaemia. Br. J. Haematol. 105, 883–893 (1999). · DOI
  142. Ball, S. E. et al. Progressive telomere shortening in aplastic anemia. Blood 91, 3582–3592 (1998). · DOI
  143. Shay, J. W. & Wright, W. E. Telomeres and telomerase: three decades of progress. Nat. Rev. Genet. 20, 299–309 (2019). · DOI · Paper page
  144. Savage, S. A. Beginning at the ends: telomeres and human disease. F1000Res https://doi.org/10.12688/f1000research.14068.1 (2018). · DOI · Paper page
  145. Podlevsky, J. D., Bley, C. J., Omana, R. V., Qi, X. & Chen, J. J. The telomerase database. Nucleic Acids Res. 36, D339–D343 (2008). · DOI
  146. Guo, Y. et al. Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1. Blood 124, 2767–2774 (2014). · DOI
  147. Bisht, K., Smith, E. M., Tesmer, V. M. & Nandakumar, J. Structural and functional consequences of a disease mutation in the telomere protein TPP1. Proc. Natl Acad. Sci. USA 113, 13021–13026 (2016). · DOI
  148. Keller, R. B. et al. CTC1 mutations in a patient with dyskeratosis congenita. Pediatr. Blood Cancer 59, 311–314 (2012). · DOI · Paper page
  149. Anderson, B. H. et al. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat. Genet. 44, 338–342 (2012). · DOI
  150. Simon, A. J. et al. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. J. Exp. Med. 213, 1429–1440 (2016). · DOI
  151. Gu, P. & Chang, S. Functional characterization of human CTC1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus. Aging Cell 12, 1100–1109 (2013). · DOI
  152. Wang, Y. & Chai, W. Pathogenic CTC1 mutations cause global genome instabilities under replication stress. Nucleic Acids Res. 46, 3981–3992 (2018). · DOI
  153. Maciejowski, J. & de Lange, T. Telomeres in cancer: tumour suppression and genome instability. Nat. Rev. Mol. Cell Biol. 18, 175–186 (2017). · DOI · Paper page
  154. Makarov, V. L., Lejnine, S., Bedoyan, J. & Langmore, J. P. Nucleosomal organization of telomere-specific chromatin in rat. Cell 73, 775–787 (1993). · DOI
  155. Tommerup, H., Dousmanis, A. & de Lange, T. Unusual chromatin in human telomeres. Mol. Cell. Biol. 14, 5777–5785 (1994).
  156. Wu, P. & de Lange, T. No overt nucleosome eviction at deprotected telomeres. Mol. Cell. Biol. 28, 5724–5735 (2008). · DOI
  157. Galati, A. et al. The human telomeric protein TRF1 specifically recognizes nucleosomal binding sites and alters nucleosome structure. J. Mol. Biol. 360, 377–385 (2006). · DOI
  158. Galati, A. et al. TRF2 controls telomeric nucleosome organization in a cell cycle phase-dependent manner. PLoS ONE 7, e34386 (2012). · DOI
  159. Soman, A. et al. The human telomeric nucleosome displays distinct structural and dynamic properties. Nucleic Acids Res. 48, 5383–5396 (2020). · DOI
  160. Ichikawa, Y., Morohashi, N., Nishimura, Y., Kurumizaka, H. & Shimizu, M. Telomeric repeats act as nucleosome-disfavouring sequences in vivo. Nucleic Acids Res. 42, 1541–1552 (2014). · DOI
  161. James, T. C. et al. Distribution patterns of Hp1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Eur. J. Cell Biol. 50, 170–180 (1989).
  162. 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). · DOI
  163. Garcia-Cao, M., O’Sullivan, R., Peters, A. H., Jenuwein, T. & Blasco, M. A. Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat. Genet. 36, 94–99 (2004). · DOI
  164. Arnoult, N., Van Beneden, A. & Decottignies, A. Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1α. Nat. Struct. Mol. Biol. 19, 948–956 (2012). · DOI
  165. Blasco, M. A. The epigenetic regulation of mammalian telomeres. Nat. Rev. Genet. 8, 299–309 (2007). · DOI · Paper page
  166. Dejardin, J. & Kingston, R. E. Purification of proteins associated with specific genomic loci. Cell 136, 175–186 (2009). · DOI
  167. Grolimund, L. et al. A quantitative telomeric chromatin isolation protocol identifies different telomeric states. Nat. Commun. 4, 2848 (2013). · DOI
  168. Pfeiffer, V., Crittin, J., Grolimund, L. & Lingner, J. The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening. EMBO J. 32, 2861–2871 (2013). · DOI
  169. Ribes-Zamora, A., Indiviglio, S. M., Mihalek, I., Williams, C. L. & Bertuch, A. A. TRF2 interaction with Ku heterotetramerization interface gives insight into c-NHEJ prevention at human telomeres. Cell Rep. 5, 194–206 (2013). · DOI
  170. Fisher, T. S. & Zakian, V. A. Ku: a multifunctional protein involved in telomere maintenance. DNA Repair 4, 1215–1226 (2005). · DOI
  171. McKay, S. J. & Cooke, H. hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. Nucleic Acids Res. 20, 6461–6464 (1992). · DOI
  172. Ishikawa, F., Matunis, M. J., Dreyfuss, G. & Cech, T. R. Nuclear proteins that bind the pre-mRNA 3′ splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n. Mol. Cell Biol. 13, 4301–4310 (1993).
  173. LaBranche, H. et al. Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. Nat. Genet. 19, 199–202 (1998). · DOI
  174. Potjer, T. P. et al. Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families. Int. J. Cancer 144, 2453–2464 (2019). · DOI
  175. Guacci, A. et al. Identification of a novel truncating mutation in PALB2 gene by a multigene sequencing panel for mutational screening of breast cancer risk-associated and related genes. J. Clin. Laboratory Anal. 32, e22418 (2018). · DOI
  176. Aoude, L. G. et al. Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma. J. Natl Cancer Inst. 107, dju408 (2015). · DOI
  177. Vulliamy, T. et al. Telomere length measurement can distinguish pathogenic from non-pathogenic variants in the shelterin component, TIN2. Clin. Genet. 81, 76–81 (2012). · DOI
  178. Sasa, G. S., Ribes-Zamora, A., Nelson, N. D. & Bertuch, A. A. Three novel truncating TINF2 mutations causing severe dyskeratosis congenita in early childhood. Clin. Genet. 81, 470–478 (2012). · DOI
  179. Vulliamy, T. J. et al. Differences in disease severity but similar telomere lengths in genetic subgroups of patients with telomerase and shelterin mutations. PLoS ONE 6, e24383 (2011). · DOI
  180. Robles-Espinoza, C. D. et al. POT1 loss-of-function variants predispose to familial melanoma. Nat. Genet. 46, 478–481 (2014). · DOI · Paper page
  181. Polvi, A. et al. Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts. Am. J. Hum. Genet. 90, 540–549 (2012). · DOI
  182. Netravathi, M. et al. Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation. BMC Med. Genet. 16, 5 (2015). · DOI
  183. Walne, A. J. et al. Mutations in the telomere capping complex in bone marrow failure and related syndromes. Haematologica 98, 334–338 (2013). · DOI

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Metadata

Authors
Lim, C. J., & Cech, T. R.
ORCID
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2021-02-09
Volume
22
Issue
4
Pages
283-298
ISSN
  • 1471-0072
  • 1471-0080
DOI
10.1038/s41580-021-00328-y
PMC
PMC8221230
Cited by
273
References
21
Language
en
Update notices
correction (2021-02-19)
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