Shelterin: The protein complex that shapes and safeguards human telomeres

Genes and Development

Volumn 19, Issue 18, 2005, Pages 2100-2110

  De Lange, Titia ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

Author keywords

Cancer; DNA damage response; Shelterin; Telomerase; Telomere

Indexed keywords

ATM PROTEIN; CHROMOSOME PROTEIN; CIS ACTING ELEMENT; COHESIN; CONDENSIN; EXCISION REPAIR CROSS COMPLEMENTING PROTEIN 1; HELICASE; MRE11 PROTEIN; POLYDEOXYRIBONUCLEOTIDE SYNTHASE; PROTEIN; PROTEIN INHIBITOR; PROTEIN POT1; PROTEIN TIN2; PROTEIN TPP1; RAD51 PROTEIN; SHELTERIN; TANKYRASE; TELOMERASE; TELOMERIC REPEAT BINDING FACTOR 1; TELOMERIC REPEAT BINDING FACTOR 2; UNCLASSIFIED DRUG;

ANAPHASE; AUTOPHOSPHORYLATION; CELL CYCLE S PHASE; CHROMOSOME SEGREGATION; CROSS LINKING; DICENTRIC CHROMOSOME; DNA DAMAGE; DNA REPAIR; DNA SEQUENCE; DNA SYNTHESIS; ENZYME INHIBITION; EXCISION REPAIR; GENOME; HOMOLOGOUS RECOMBINATION; HUMAN; MISMATCH REPAIR; MITOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REGULATORY DNA SEQUENCE; RESTRICTION FRAGMENT; REVIEW; SENESCENCE; SISTER CHROMATID EXCHANGE; TELOMERE;

ANTIGENS, SURFACE; BINDING SITES; CELL ADHESION MOLECULES; CHROMOSOMAL INSTABILITY; DNA DAMAGE; ENDOPEPTIDASES; HUMANS; MEMBRANE GLYCOPROTEINS; MODELS, BIOLOGICAL; MULTIPROTEIN COMPLEXES; PEPTIDE HYDROLASES; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; PROTEIN SUBUNITS; PROTEINS; RAP1 GTP-BINDING PROTEINS; TANDEM REPEAT SEQUENCES; TELOMERE; TELOMERE-BINDING PROTEINS; TELOMERIC REPEAT BINDING PROTEIN 1; TELOMERIC REPEAT BINDING PROTEIN 2;

EID: 24944460598     PISSN: 08909369     EISSN: None     Source Type: Journal    
DOI: 10.1101/gad.1346005     Document Type: Review

References (85)

1. Bai, Y. and Murnane, J.P. 2003. Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein. Hum. Genet. 113: 337-347.
2. Bailey, S.M., Brenneman, M.A., and Goodwin, E.H. 2004. Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res. 32: 3743-3751.
3. Bakkenist, C.J. and Kastan, M.B. 2003. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499-506.
4. Baumann, P. and Cech, T.R. 2001. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292: 1171-1175.
5. Bechter, O.E., Zou, Y., Walker, W., Wright, W.E., and Shay, J.W. 2004. Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition. Cancer Res. 64: 3444-3451.
6. Bianchi, A., Smith, S., Chong, L., Elias, P., and de Lange, T. 1997. TRF1 is a dimer and bends telomeric DNA. EMBO J. 16: 1785-1794.
7. Bianchi, A., Stansel, R.M., Fairall, L., Griffith, J.D., Rhodes, D., and de Lange, T. 1999. TRF1 binds a bipartite telomeric site with extreme spatial flexibility. EMBO J. 18: 5735-5744.
8. Bilaud, T., Brun, C., Ancelin, K., Koering, C.E., Laroche, T., and Gilson, E. 1997. Telomeric localization of TRF2, a novel human telobox protein. Nat. Genet. 17: 236-239.
9. Broccoli, D., Smogorzewska, A., Chong, L., and de Lange, T. 1997. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat. Genet. 17: 231-235.
10. Celli, G. and de Lange, T. 2005. DNA processing not required for ATM-mediated telomere damage response after TRF2 deletion. Nat. Cell. Biol. 7: 712-718.
11. Cesare, A.J. and Griffith, J.D. 2004. Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol. Cell. Biol. 24: 9948-9957.
12. Chang, W., Dynek, J.N., and Smith, S. 2003. TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres. Genes & Dev. 17: 1328-1333.
13. Chikashige, Y. and Hiraoka, Y. 2001. Telomere binding of the Rap1 protein is required for meiosis in fission yeast. Curr. Biol. 11: 1618-1623.
14. Chin, L., Artandi, S.E., Shen, Q., Tam, A., Lee, S.L., Gottlieb, G.J., Greider, C.W., and DePinho, R.A. 1999. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97: 527-538.
15. Chong, L., van Steensel, B., Broccoli, D., Erdjument-Bromage, H., Hanish, J., Tempst, P., and de Lange, T. 1995. A human telomeric protein. Science 270: 1663-1667.
16. Cooper, J.P., Watanabe, Y., and Nurse, P. 1998. Fission yeast Taz1 protein is required for meiotic telomere clustering and recombination. Nature 392: 828-831.
17. Court, R., Chapman, L., Fairall, L., and Rhodes, D. 2005. How the human telomeric proteins TRF1 and TRF2 recognize telomeric DNA: A view from high-resolution crystal structures. EMBO Rep. 6: 39-45.
18. Crabbe, L., Verdun, R.E., Haggblom, C.I., and Karlseder, J. 2004. Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306: 1951-1953.
19. d'Adda di Fagagna, F., Hande, M.P., Tong, W.M., Roth, D., Lansdorp, P.M., Wang, Z.Q., and Jackson, S.P. 2001. Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells. Curr. Biol. 11: 1192-1196.
20. d'Adda di Fagagna, F., Reaper, P.M., Clay-Farrace, L., Fiegler, H., Carr, P., Von Zglinicki, T., Saretzki, G., Carter, N.P., and Jackson, S.P. 2003. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426: 194-198.
21. Dantzer, F., Giraud-Panis, M.J., Jaco, I., Ame, J.C., Schultz, I., Blasco, M., Koering, C.E., Gilson, E., Menissier-de Murcia, J., de Murcia, G., et al. 2004. Functional interaction between poly(ADP-Ribose) polymerase 2 (PARP-2) and TRF2: PARP activity negatively regulates TRF2. Mol. Cell. Biol. 24: 1595-1607.
22. de Lange, T. 2001. Telomere capping - one strand fits all. Science 292: 1075-1076.
23. _. 2002. Protection of mammalian telomeres. Oncogene 21: 532-540.
24. de Lange, T. and Petrini, J. 2000. A new connection at human telomeres: Association of the Mre11 complex with TRF2. Cold Spring Harb. Symp. Quant. Biol. LXV: 265-273.
25. Dynek, J.N. and Smith, S. 2004. Resolution of sister telomere association is required for progression through mitosis. Science 304: 97-100.
26. Griffith, J., Bianchi, A., and de Lange, T. 1998. TRF1 promotes parallel pairing of telomeric tracts in vitro. J. Mol. Biol. 278: 79-88.
27. Griffith, J.D., Comeau, L., Rosenfield, S., Stansel, R.M., Bianchi, A., Moss, H., and de Lange, T. 1999. Mammalian telomeres end in a large duplex loop. Cell 97: 503-514.
28. Hanaoka, S., Nagadoi, A., and Nishimura, Y. 2005. Comparison between TRF2 and TRF1 of their telomeric DNA-bound structures and DNA-binding activities. Protein Sci. 14: 119-130.
29. Hardy, C.F., Sussel, L., and Shore, D. 1992. A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation. Genes & Dev. 6: 801-814.
30. Herbig, U., Jobling, W.A., Chen, B.P., Chen, D.J., and Sedivy, J.M. 2004. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol. Cell 14: 501-513.
31. Hockemeyer, D., Sfeir, A.J., Shay, J.W., Wright, W.E., and de Lange, T. 2005. POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes end. EMBO J. 20: 2667-2678.
32. Houghtaling, B.R., Cuttonaro, L., Chang, W., and Smith, S. 2004. A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2. Curr. Biol. 14: 1621-1631.
33. Hsu, H.L., Gilley, D., Blackburn, E.H., and Chen, D.J. 1999. Ku is associated with the telomere in mammals. Proc. Natl. Acad. Sci. 96: 12454-12458.
34. Hsu, H.L., Gilley, D., Galande, S.A., Hande, M.P., Allen, B., Kim, S.H., Li, G.C., Campisi, J., Kohwi-Shigematsu, T., and Chen, D.J. 2000. Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes & Dev. 14: 2807-2812.
35. Huber, M.D., Lee, D.C., and Maizels, N.P. 2002. G4 DNA unwinding by BLM and Sgs1p: Substrate specificity and substrate-specific inhibition. Nucleic Acids Res. 30: 3954-3961.
36. Huyen, Y., Zgheib, O., Ditullio Jr., R.A., Gorgoulis, V.G., Zacharatos, P., Petty, T.J., Sheston, E.A., Mellert, H.S., Stavridi, E.S., and Halazonetis, T.D. 2004. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432: 406-411.
37. Jacobs, J.J. and de Lange, T. 2004. Significant role for p16(INK4a) in p53-Independent telomere-directed senescence. Curr. Biol. 14: 2302-2308.
38. Kaminker, P.G., Kim, S.H., Taylor, R.D., Zebarjadian, Y., Funk, W.D., Morin, G.B., Yaswen, P., and Campisi, J. 2001. TANK2, a new TRF1-associated PARP, causes rapid induction of cell death upon overexpression. J. Biol. Chem. 276: 35891-35899.
39. Kanoh, J. and Ishikawa, F. 2001. spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast. Curr. Biol. 11: 1624-1630.
40. Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., and de Lange, T. 1999. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283: 1321-1325.
41. Karlseder, J., Hoke, K., Mirzoeva, O.K., Bakkenist, C., Kastan, M.B., Petrini, J.H., and de Lange, T. 2004. The telomeric protein TRF2 binds the ATM kinase and can inhibit the ATM-dependent DNA damage response. PLoS Biol. 2: E240.
42. Kelleher, C., Kurth, I., and Lingner, J. 2005. Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro. Mol. Cell. Biol. 25: 808-818.
43. Kim, S.H., Kaminker, P., and Campisi, J. 1999. TIN2, a new regulator of telomere length in human cells. Nat. Genet. 23: 405-412.
44. Kim, S.H., Han, S., You, Y.H., Chen, D.J., and Campisi, J. 2003. The human telomere-associated protein TIN2 stimulates interactions between telomeric DNA tracts in vitro. EMBO Rep. 4: 685-691.
45. Kim, S.H., Beausejour, C., Davalos, A.R., Kaminker, P., Heo, S.J., and Campisi, J. 2004. TIN2 mediates functions of TRF2 at human telomeres. J. Biol. Chem. 279: 43799-43804.
46. Lei, M., Podell, E.R., and Cech, T.R. 2004. Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat. Struct. Mol. Biol. 11: 1223-1229.
47. Lei, M., Zaug, A.J., Podell, E.R., and Cech, T.R. 2005. Switching human telomerase on and off with hPOT1 protein in vitro. J. Biol. Chem. 280: 20449-20456.
48. Li, B., Oestreich, S., and de Lange, T. 2000. Identification of human Rap1: Implications for telomere evolution. Cell 101: 471-483.
49. Liu, D., O'Connor, M.S., Qin, J., and Songyang, Z. 2004a. Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J. Biol. Chem. 279: 51338-51342.
50. Liu, D., Safari, A., O'Connor, M.S., Chan, D.W., Laegeler, A., Qin, J., and Songyang, Z. 2004b. PTOP interacts with POT1 and regulates its localization to telomeres. Nat. Cell. Biol. 6: 673-680.
51. Loayza, D. and de Lange, T. 2003. POT1 as a terminal transducer of TRF1 telomere length control. Nature 424: 1013-1018.
52. Loayza, D., Parsons, H., Donigian, J., Hoke, K., and de Lange, T. 2004. 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.
53. Londono-Vallejo, J.A., Der-Sarkissian, H., Cazes, L., Bacchetti, S., and Reddel, R.R. 2004. Alternative lengthening of telomeres is characterized by high rates of telomeric exchange. Cancer Res. 64: 2324-2327.
54. Machwe, A., Xiao, L., and Orren, D.K. 2004. TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA. Oncogene 23: 149-156.
55. Makarov, V.L., Hirose, Y., and Langmore, J.P. 1997. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 88: 657-666.
56. Mattern, K.A., Swiggers, S.J., Nigg, A.L., Lowenberg, B., Houtsmuller, A.B., and Zijlmans, J.M. 2004. Dynamics of protein binding to telomeres in living cells: Implications for telomere structure and function. Mol. Cell. Biol. 24: 5587-5594.
57. Neumann, A.A. and Reddel, R.R. 2002. Telomere maintenance and cancer-look, no telomerase. Nat. Rev. Cancer 2: 879-884.
58. Nikitina, T. and Woodcock, C.L. 2004. Closed chromatin loops at the ends of chromosomes. J. Cell. Biol. 166: 161-165.
59. O'Connor, M.S., Safari, A., Liu, D., Qin, J., and Songyang, Z. 2004. The human Rap1 protein complex and modulation of telomere length. J. Biol. Chem. 279: 28585-28591.
60. Opresko, P.L., Von Kobbe, C., Laine, J.P., Harrigan, J., Hickson, I.D., and Bohr, V.A. 2002. Telomere binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J. Biol. Chem. 277: 41110-41119.
61. Opresko, P.L., Otterlei, M., Graakjaer, J., Bruheim, P., Dawut, L., Kolvraa, S., May, A., Seidman, M.M., and Bohr, V.A. 2004. The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Mol. Cell 14: 763-774.
62. Sanders, S.L., Portoso, M., Mata, J., Bahler, J., Allshire, R.C., and Kouzarides, T. 2004. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 119: 603-614.
63. Sfeir, A.J., Chai, W., Shay, J.W., and Wright, W.E. 2005. Telomere-end processing the terminal nucleotides of human chromosomes. Mol. Cell 18: 131-138.
64. Shore, D. 1994. RAP1: A protean regulator in yeast. Trends Genet. 10: 408-412.
65. Silverman, J., Takai, H., Buonomo, S.B., Eisenhaber, F., and de Lange, T. 2004. Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint. Genes & Dev. 18: 2108-2119.
66. Smith, S. and de Lange, T. 2000. Tankyrase promotes telomere elongation in human cells. Curr. Biol. 10: 1299-1302.
67. Smith, S., Giriat, I., Schmitt, A., and de Lange, T. 1998. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282: 1484-1487.
68. Smogorzewska, A. and de Lange, T. 2002. Different telomere damage signaling pathways in human and mouse cells. EMBO J. 21: 4338-4348.
69. _. 2004. Regulation of telomerase by telomeric proteins. Annu. Rev. Biochem. 73: 177-208.
70. Smogorzewska, A., Karlseder, J., Holtgreve-Grez, H., Jauch, A., and de Lange, T. 2002. DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2. Curr. Biol. 12: 1635.
71. Stansel, R.M., de Lange, T., and Griffith, J.D. 2001. T-loop assembly in vitro involves binding of TRF2 near the 3′ telomeric overhang. EMBO J. 20: E5532-E5540.
72. Stavropoulos, D.J., Bradshaw, P.S., Li, X., Pasic, I., Truong, K., Ikura, M., Ungrin, M., and Meyn, M.S. 2002. The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis. Hum. Mol. Genet. 11: 3135-3144.
73. Sun, H., Karow, J.K., Hickson, I.D., and Maizels, N.P. 1998. The Bloom's syndrome helicase unwinds G4 DNA. J. Biol. Chem. 273: 27587-27592.
74. Takai, H., Smogorzewska, A., and de Lange, T. 2003. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13: 1549-1556.
75. Tarsounas, M., Munoz, P., Claas, A., Smiraldo, P.G., Pittman, D.L., Blasco, M.A., and West, S.C. 2004. Telomere maintenance requires the RAD51D recombination/repair protein. Cell 117: 337-347.
76. van Steensel, B., Smogorzewska, A., and de Lange, T. 1998. TRF2 protects human telomeres from end-to-end fusions. Cell 92: 401-413.
77. Wang, R.C., Smogorzewska, A., and de Lange, T. 2004. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119: 355-368.
78. Xu, L. and Blackburn, E.H. 2004. Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules. J. Cell. Biol. 167: 819-830.
79. Yang, Q., Zheng, Y.L., and Harris, C.C. 2005. POT1 and TRF2 cooperate to maintain telomeric integrity. Mol. Cell. Biol. 25: 1070-1080.
80. Yankiwski, V., Marciniak, R.A., Guarente, L., and Neff, N.F. 2000. Nuclear structure in normal and Bloom syndrome cells. Proc. Natl. Acad. Sci. 97: 5214-5219.
81. Ye, J.Z. and de Lange, T. 2004. TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex. Nat. Genet. 36: 618-623.
82. Ye, J.Z., Donigian, J.R., Van Overbeek, M., Loayza, D., Luo, Y., Krutchinsky, A.N., Chait, B.T., and de Lange, T. 2004a. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J. Biol. Chem. 279: 47264-47271.
83. Ye, J.Z., Hockemeyer, D., Krutchinsky, A.N., Loayza, D., Hooper, S.M., Chait, B.T., and de Lange, T. 2004b. POT1-interacting protein PIP1: A telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes & Dev. 18: 1649-1654.
84. Zhong, Z., Shiue, L., Kaplan, S., and de Lange, T. 1992. A mammalian factor that binds telomeric TTAGGG repeats in vitro. Mol. Cell. Biol. 12: 4834-4843.
85. Zhu, X.D., Niedernhofer, L., Kuster, B., Mann, M., Hoeijmakers, J.H., and de Lange, T. 2003. ERCC1/XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol. Cell 12: 1489-1498.