Functional links between telomeres and proteins of the DNA-damage response

Genes and Development

Volumn 18, Issue 15, 2004, Pages 1781-1799

  D'Adda Di Fagagna, Fabrizio ^a   Teo, Soo Hwang ^b   Jackson, Stephen P ^b  

^a FIRC INSTITUTE OF MOLECULAR ONCOLOGY   (Italy)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Checkpoint; DNA repair; DNA damage response; Senescence; Telomere

Indexed keywords

ATM PROTEIN; DOUBLE STRANDED DNA; MRE11 PROTEIN; PHOSPHOTRANSFERASE; RAD50 PROTEIN; RAD51 PROTEIN; RAD52 PROTEIN; TELOMERASE;

APOPTOSIS; CAENORHABDITIS ELEGANS; CELL CYCLE; DNA DAMAGE; DNA HELIX; DNA REPAIR; DNA STRAND BREAKAGE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SACCHAROMYCES CEREVISIAE; SCHIZOSACCHAROMYCES POMBE; SENESCENCE; TELOMERE; TRYPANOSOMA;

ANIMALS; DNA; DNA DAMAGE; DNA REPAIR; DNA-BINDING PROTEINS; HUMANS; NUCLEAR PROTEINS; TELOMERE;

CAENORHABDITIS; CAENORHABDITIS ELEGANS; SACCHAROMYCES; SACCHAROMYCES CEREVISIAE; SCHIZOSACCHAROMYCES; SCHIZOSACCHAROMYCES POMBE; TRYPANOSOMA;

EID: 3543056880     PISSN: 08909369     EISSN: None     Source Type: Journal    
DOI: 10.1101/gad.1214504     Document Type: Review

References (195)

1. Adams, I.R. and McLaren, A. 2004. Identification and characterisation of mRif1: A mouse telomere-associated protein highly expressed in germ cells and embryo-derived pluripotent stem cells. Dev. Dyn. 229: 733-744.
2. Ahmed, S. and Hodgkin, J. 2000. MRT-2 checkpoint protein is required for germline immortality and telomere replication in C-elegans. Nature 403: 159-164.
3. Ahmed, S., Alpi, A., Hengartner, M.O., and Gartner, A. 2001. C. elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein. Curr. Biol. 11: 1934-1944.
4. Bailey, S.M., Cornforth, M.N., Kurimasa, A., Chen, D.J., and Goodwin E.H. 2001. Strand-specific postreplicative processing of mammalian telomeres. Science 293: 2462-2465.
5. Bailey, S.M., Brenneman, M.A., Halbrook, J., Nickoloff, J.A., Ullrich, R.L., and Goodwin, E.H. 2004. The kinase activity of DNA-PK is required to protect mammalian telomeres. DNA Repair 3: 225-233.
6. Bakkenist, C.J. and Kastan, M.B. 2003. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499-506.
7. Bakkenist, C.J., Drissi, R., Wu, J., Kastan, M.B., and Dome, J.S. 2004. Disappearance of the telomere dysfunction-induced stress response in fully senescent cells. Cancer Res. 64: 3748-3752.
8. Bartek, J. and Lukas, J. 2003. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3: 421-429.
9. Baumann, P. and Cech, T.R. 2000. Protection of telomeres by the Ku protein in fission yeast. Mol. Biol. Cell 11: 3265-3275.
10. -. 2001. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292: 1171-1175.
11. Benard, C., McCright, B., Zhang, Y., Felkai, S., Lakowski, B., and Hekimi, S. 2001. The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length. Development 128: 4045-4055.
12. Bertuch, A.A. and Lundblad, V. 2003. The Ku heterodimer performs separable activities at double-strand breaks and chromosome termini. Mol. Cell. Biol. 23: 8202-8215.
13. Blackburn, E.H. 2000. Telomere states and cell fates. Nature 408: 53-56.
14. Blasco, M.A. 2002. Mouse models to study the role of telomeres in cancer, aging and DNA repair. Eur. J. Cancer 38: 2222-2228.
15. Bomgarden, R.D., Yean, D., Yee, M.C., and Cimprich, K.A. 2004. A novel protein activity mediates DNA binding of an ATR-ATRIP complex. J. Biol. Chem. 279: 13346-13353.
16. Booth, C., Griffith, E., Brady, G., and Lydall, D. 2001. Quantitative amplification of single-stranded DNA (QAOS) demonstrates that cdc13-1 mutants generate ssDNA in a telomere to centromere direction. Nucleic Acids Res. 29: 4414-4422.
17. Boulton, S.J. and Jackson, S.P. 1996. Identification of a Saccharomyces cerevisiae Ku80 homologue: Roles in DNA double-strand break rejoining and in telomeric maintenance. Nucleic Acids Res. 24: 4639-4648.
18. -. 1998. Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing. EMBO J. 17: 1819-1828.
19. Brown, E.J. and Baltimore, D. 2000. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes & Dev. 14: 397-402.
20. Bundock, P. and Hooykaas, P. 2002. Severe developmental defects, hypersensitivity to DNA-damaging agents, and lengthened telomeres in Arabidopsis MRE11 mutants. Plant Cell 14: 2451-2462.
21. Bundock, P., van Attikum, H., and Hooykaas, P. 2002. Increased telomere length and hypersensitivity to DNA damaging agents in an Arabidopsis KU70 mutant. Nucleic Acids Res. 30: 3395-3400.
22. Chahwan, C., Nakamura, T.M., Sivakumar, S., Russell, P., and Rhind, N. 2003. The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint. Mol. Cell. Biol. 23: 6564-6573.
23. Chakhparonian, M. and Wellinger, R.J. 2003. Telomere maintenance and DNA replication: How closely are these two connected? Trends Genet. 19: 439-446.
24. Chan, S.W.L., Chang, J., Prescott, J., and Blackburn, E.H. 2001. Altering telomere structure allows telomerase to act in yeast lacking ATM kinases. Curr. Biol. 11: 1240-1250.
25. Chen, Q., Ijpma, A., and Greider, C.W. 2001. Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. Mol. Cell. Biol. 21: 1819-1827.
26. 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.
27. Colgin, L.M., Baran, K., Baumann, P., Cech, T.R., and Reddel, R.R. 2003. Human POT1 facilitates telomere elongation by telomerase. Curr. Biol. 13: 942-946.
28. Corda, Y., Schramke, V., Longhese, M.P., Smokvina, T., Paciotti, V., Brevet, V., Gilson, E., and Geli, V. 1999. Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions. Nat. Genet. 21: 204-208.
29. Cosgrove, A.J., Nieduszynski, C.A., and Donaldson, A.D. 2002. Ku complex controls the replication time of DNA in telomere regions. Genes & Dev. 16: 2485-2490.
30. Craven, R.J. and Petes, T.D. 1999. Dependence of the regulation of telomere length on the type of subtelomeric repeat in the yeast Saccharomyces cerevisiae. Genetics 152: 1531-1541.
31. d'Adda di Fagagna, F., Hande, M.P., Tong, W.-M., Lansdorp, P.M., Wang, Z.-Q., and Jackson, S.P. 1999. Functions of poly-(ADP-ribose) polymerase in controlling telomere length and chromosomal stability. Nat. Genet. 23: 76-80.
32. 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.
33. 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.
34. Dahlen, M., Olsson, T., Kanter-Smoler, G., Ramne, A., and Sunnerhagen, P. 1998. Regulation of telomere length by checkpoint genes in Schizosaccharomyces pombe. Mol. Biol. Cell 9: 611-621.
35. D'Amours, D. and Jackson, S.P. 2001. The yeast Xrs2 complex functions in S phase checkpoint regulation. Genes & Dev. 15: 2238-2249.
36. -. 2002. The Mre11 complex: At the crossroads of DNA repair and checkpoint signalling. Nat. Rev. Mol. Cell Biol. 3: 317-327.
37. D'Amours, D., Desnoyers, S., D'Silva, I., and Poirier, G.G. 1999. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem. J. 342: 249-268.
38. de Bruin, D., Zaman, Z., Liberatore, R.A., and Ptashne, M. 2001. Telomere looping permits gene activation by a downstream UAS in yeast. Nature 409: 109-113.
39. de Laat, W.L., Jaspers, N.G.J., and Hoeijmakers, J.H.J. 1999. Molecular mechanism of nucleotide excision repair. Genes & Dev. 13: 768-785.
40. Diede, S.J. and Gottschling, D.E. 1999. Telomerase-mediated telomere addition in vivo requires DNA primase and DNA polymerases α and δ. Cell 99: 723-733.
41. -. 2001. Exonuclease activity is required for sequence addition and Cdc13p loading at a de novo telomere. Curr. Biol. 11: 1336-1340.
42. Downs, J.A. and Jackson, S.P. 2004. A means to a DNA end: The many roles of Ku. Nat. Rev. Mol. Cell Biol. 5: 367-378.
43. Downs, J.A., Kosmidou, E., Morgan, A., and Jackson, S.P. 2003. Suppression of homologous recombination by the Saccharomyces cerevisiae linker histone. Mol. Cell 11: 1685-1692.
44. Driller, L., Wellinger, R.J., Larrivee, M., Kremmer, E., Jaklin, S., and Feldmann, H.M. 2000. A short C-terminal domain of Yku70p is essential for telomere maintenance. J. Biol. Chem. 275: 24921-24927.
45. DuBois, M.L., Haimberger, Z.W., McIntosh, M.W., and Gottschling, D.E. 2002. A quantitative assay for telomere protection in Saccharomyces cerevisiae. Genetics 161: 995-1013.
46. Dunham, M.A., Neumann, A.A., Fasching, C.L., and Reddel, R.R. 2000. Telomere maintenance by recombination in human cells. Nature Genet. 26: 447-450.
47. Enomoto, S., Glowczewski, L., and Berman, J. 2002. MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae. Mol. Biol. Cell 13: 2626-2638.
48. Espejel, S., Franco, S., Rodríguez-Perales, S., Bouffler, S.D., Cigudosa, J.C., and Blasco, M.A. 2002a. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. EMBO J. 21: 2207-2219.
49. Espejel, S., Franco, S., Sgura, A., Gae, D., Bailey, S.M., Taccioli, G.E., and Blasco, M.A. 2002b. Functional interaction between DNA-PKcs and telomerase in telomere length maintenance. EMBO J. 21: 6275-6287.
50. Fernandez-Capetillo, O. and Nussenzweig, A. 2004. Linking histone deacetylation with the repair of DNA breaks. Proc. Natl Acad Sci 101: 1427-1428.
51. Fernandez-Capetillo, O., Liebe, B., Scherthan, H., and Nussenzweig, A. 2003. H2AX regulates meiotic telomere clustering. J. Cell Biol. 163: 15-20.
52. Ferreira, M.G. and Cooper, J.P. 2001. The fission yeast Taz1 protein protects chromosomes from Ku-dependent end-to-end fusions. Mol. Cell 7: 55-63.
53. Figueiredo, L.M., Freitas-Junior, L.H., Bottius, E., Olivo-Marin, J.C., and Scherf, A. 2002. A central role for Plasmodium falciparum subtelomeric regions in spatial positioning and telomere length regulation. EMBO J. 21: 815-824.
54. Foray, N., Marot, D., Gabriel, A., Randrianarison, V., Carr, A.M., Perricaudet, M., Ashworth, A., and Jeggo, P. 2003. A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. EMBO J. 22: 2860-2871.
55. Friedberg, E.C., Walker, G.C., and Siede, W. 1995. DNA repair and mutagenesis. ASM Press, Washington, D.C.
56. Gallego, M.E. and White, C.I. 2001. RAD50 function is essential for telomere maintenance in Arabidopsis. Proc. Nat. Acad. Sci. 98: 1711-1716.
57. Garvik, B., Carson, M., and Hartwell, L. 1995. Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol. Cell. Biol. 15: 6128-6138.
58. Gilbert, C.S., Green, C.M., and Lowndes, N.F. 2001. Budding yeast Rad9 is an ATP-dependent Rad53 activating machine. Mol. Cell 8: 129-136.
59. Gilley, D., Tanaka, H., Hande, M.P., Kurimasa, A., Li, G.C., and Chen, D.J. 2001. DNA-PKcs is critical for telomere capping. Proc. Nat. Acad. Sci. 98: 15084-15088.
60. Goldberg, M., Stucki, M., Falck, J., D'Amours, D., Rahman, D., Pappin, D., Bartek, J., and Jackson, S.P. 2003. MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421: 952-956.
61. Gotta, M., Laroche, T., Formenton, A., Maillet, L., Scherthan, H., and Gasser, S.M. 1996. The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild type Saccharomyces cerevisiae. J. Cell Biol. 134: 1349-1363.
62. Goytisolo, F.A., Samper, E., Martin-Caballero, J., Finnon, P., Herrera, E., Flores, J.M., Bouffler, S.D., and Blasco, M.A. 2000. Short telomeres result in organismal hypersensitivity to ionizing radiation in mammals. J. Exp. Med. 192: 1625-1636.
63. Grandin, N. and Charbonneau, M. 2003. The Rad51 pathway of telomerase-independent maintenance of telomeres can amplify TG1-3 sequences in yku and cdc13 mutants of Saccharomyces cerevisiae. Mol. Cell. Biol. 23: 3721-3734.
64. Grandin, N., Reed, S.I., and Charbonneau, M. 1997. Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes & Dev. 11: 512-527.
65. Grandin, N., Damon, C., and Charbonneau, M. 2001a. Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination. EMBO J. 20: 6127-6139.
66. -. 2001b. Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13. EMBO J. 20: 1173-1183.
67. Gravel, S. and Wellinger, R.J. 2002. Maintenance of double-stranded telomeric repeats as the critical determinant for cell viability in yeast cells lacking Ku. Mol. Cell. Biol. 22: 2182-2193.
68. Gravel, S., Larrivée, M., Labrecque, P., and Wellinger, R.J. 1998. Yeast Ku as a regulator of chromosomal DNA end structure. Science 280: 741-744.
69. Greenwell, P.W., Kronmal, S.L., Porter, S.E., Gassenhuber, J., Obermaier, B., and Petes, T.D. 1995. TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell 82: 823-829.
70. Grenon, M., Gilbert, C., and Lowndes, N.F. 2001. Checkpoint activation in response to double-strand breaks requires the Mre11/Rad50/Xrs2 complex. Nat. Cell Biol. 3: 844-847.
71. 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.
72. Hande, M.P., Balajee, A.S., and Natarajan, A.T. 1997. Induction of telomerase activity by UV-irradiation in Chinese hamster cells. Oncogene 15: 1747-1752.
73. Hande, M.P., Lansdorp, P.M., and Natarajan, A.T. 1998. Induction of telomerase activity by in vivo X-irradiation of mouse splenocytes and its possible role in chromosome healing. Mutat. Res. 404: 205-214.
74. -/- mice and patients with ataxiatelangiectasia. Human Mol. Genet. 10: 519-528.
75. Hartsuiker, E., Vaessen, E., Carr, A.M., and Kohli, J. 2001. Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair. EMBO J. 20: 6660-6671.
76. Henson, J.D., Neumann, A.A., Yeager, T.R., and Reddel, R.R. 2002. Alternative lengthening of telomeres in mammalian cells. Oncogene 21: 598-610.
77. 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.
78. Herrmann, G., Lindahl, T., and Schar, P. 1998. Saccharomyces cerevisiae LIF1: A function involved in DNA double-strand break repair related to mammalian XRCC4. EMBO J. 17: 4188-4198.
79. 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.
80. 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.
81. IJpma, A.S. and Greider, C.W. 2003. Short telomeres induce a DNA damage response in Saccharomyces cerevisiae. Mol. Biol. Cell 14:987-1001.
82. Jaco, I., Munoz, P., Goytisolo, F., Wesoly, J., Bailey, S., Taccioli, G., and Blasco, M.A. 2003. Role of mammalian Rad54 in telomere length maintenance. Mol. Cell. Biol. 23:5572-5580.
83. Jiang, N., Benard, C.Y., Kebir, H., Shoubridge, E.A., and Hekimi, S. 2003. Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation. J. Biol. Chem. 278: 21678-21684.
84. Kanellis, P., Agyei, R., and Durocher, D. 2003. Elg1 forms an alternative PCNA-interacting RFC complex required to maintain genome stability. Curr. Biol. 13: 1583-1595.
85. 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.
86. Karlseder, J., Smogorzewska, A., and de Lange, T. 2002. Senescence induced by altered telomere state, not telomere loss. Science 295: 2446-2449.
87. Karnitz, L.M. 2004. Dial 9-1-1 for DNA damage: The Rad9-Hus1-Rad1 clamp complex. DNA Repair (Amst.) (in press).
88. Khanna, K.K. and Jackson, S.P. 2001. DNA double-strand breaks: Signaling, repair and the cancer connection. Nat. Genet. 27: 247-254.
89. Kharbanda, S., Kumar, V., Dhar, S., Pandey, P., Chen, C., Majumder, P., Yuan, Z.-M., Whang, Y., Strauss, W., Pandita, T.K., et al. 2000. Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase. Curr. Biol. 10:568-575.
90. Kota, R.S. and Runge, K.W. 1998. The yeast telomere length regulator TEL2 encodes a protein that binds to telomeric DNA. Nucleic Acids Res. 26:1528-1535.
91. Laroche, T., Martin, S.G., Gotta, M., Gorham, H.C., Pryde, F.E., Louis, E.J., and Gasser, S.M. 1998. Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr. Biol. 8: 653-656.
92. Larrivée, M., Lebel, C., and Wellinger, R.J. 2004. The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX-complex. Genes & Dev: 18: 1391-1396.
93. Le, S., Moore, J.K., Haber, J.E., and Greider, C.W. 1999. RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. Genetics 152: 143-152.
94. Lei, M., Podell, E.R., Baumann, P., and Cech, T.R. 2003. DNA self-recognition in the structure of Pot1 bound to telomeric single-stranded DNA. Nature 426: 198-203.
95. Li, B. and de Lange, T. 2003. Rap1 affects the length and heterogeneity of human telomeres. Mol. Biol. Cell 14: 5060-5068.
96. Li, G., Nelsen, C., and Hendrickson, E.A. 2002. Ku86 is essential in human somatic cells. Proc. Natl. Acad. Sci. 99: 832-837.
97. Lieber, M.R., Ma, Y., Pannicke, U., and Schwarz, K. 2003. Mechanism and regulation of human non-homologous DNA end-joining. Nat. Rev. Mol. Cell. Biol. 4: 712-720.
98. Lim, C.-S., Mian, I.S., Dernburg, A.F., and Campisi, J. 2001. C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p. Curr. Biol. 11: 1706-1710.
99. Linke, S.P., Sengupta, S., Khabie, N., Jeffries, B.A., Buchhop, S., Miska, S., Henning, W., Pedeux, R., Wang, X.W., Hofseth, L.J., et al. 2003. p53 interacts with hRAD51 and hRAD54, and directly modulates homologous recombination. Cancer Res. 63: 2596-2605.
100. Liti, G. and Louis, E.J. 2003. NEJ1 prevents NHEJ-dependent telomere fusions in yeast without telomerase. Mol. Cell 11: 1373-1378.
101. Loayza, D. and de Lange, T. 2003. POT1 as a terminal transducer of TRF1 telomere length control. Nature 424: 1013-1018.
102. Longhese, M.P., Paciotti, V., Neecke, H., and Lucchini, G. 2000. Checkpoint proteins influence telomeric silencing and length maintenance in budding yeast. Genetics 155: 1577-1591.
103. Lundblad, V. 2002. Telomere maintenance without telomerase. Oncogene 21: 522-531.
104. - senescence. Cell 73: 347-360.
105. Lustig, A.J. and Petes, T.D. 1986. Identification of yeast mutants with altered telomere structure. Proc. Natl. Acad. Sci. 83: 1398-1402.
106. Lydall, D. and Weinert, T. 1995. Yeast checkpoint genes in DNA damage processing: Implications for repair and arrest. Science 270: 1488-1491.
107. Mallory, J.C. and Petes, T.D. 2000. Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase. Proc. Natl. Acad. Sci. 97: 13749-13754.
108. Mallory, J.C., Bashkirov, V.I., Trujillo, K.M., Solinger, J.A., Dominska, M., Sung, P., Heyer, W.D., and Petes, T.D. 2003. Amino acid changes in Xrs2p, Dun1p, and Rfa2p that remove the preferred targets of the ATM family of protein kinases do not affect DNA repair or telomere length in Saccharomyces cerevisiae. DNA Repair (Amst.) 2: 1041-1064.
109. Manolis, K.G., Nimmo, E.R., Hartsuiker, E., Carr, A.M., Jeggo, P.A., and Allshire, R.C. 2001. Novel functional requirements for non-homologous DNA end joining in Schizosaccharomyces pombe. EMBO J. 20: 210-221.
110. Marcand, S., Gilson, E., and Shore, D. 1997. A protein-counting mechanism for telomere length regulation in yeast. Science 275: 986-990.
111. Maringele, L. and Lydall, D. 2002. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Δ mutants. Genes & Dev. 16: 1919-1933.
112. +. Genetics 152: 1501-1512.
113. McEachern, M.J., Krauskopf, A., and Blackburn, E.H. 2000. Telomeres and their control. Annu. Rev. Genet. 34: 331-358.
114. Mekeel, K.L., Tang, W., Kachnic, L.A., Luo, C.-M., DeFrank, J.S., and Powell, S.N. 1997. Inactivation of p53 results in high rates of homologous recombination. Oncogene 14: 1847-1857.
115. Metcalfe, J.A., Parkhill, J., Campbell, L., Stacey, M., Biggs, P., Byrd, P.J., and Taylor, A.M.R. 1996. Accelerated telomere shortening in ataxia telangiectasia. Nat. Genet. 13: 350-353.
116. Mieczkowski, P.A., Mieczkowska, J.O., Dominska, M., and Petes T.D. 2003. Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae. Proc. Natl. Acad. Sci. 100: 10854-10859.
117. Mitton-Fry, R.M., Anderson, E.M., Hughes, T.R., Lundblad, V., and Wuttke, D.S. 2002. Conserved structure for single-stranded telomeric DNA recognition. Science 296: 145-147.
118. Moreau, S., Ferguson, J.R., and Symington, L.S. 1999. The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining, or telomere maintenance. Mol. Cell. Biol. 19: 556-566.
119. Munoz-Jordan, J.L., Cross, G.A.M., de Lange, T., and Griffith, J.D. 2001. T-loops at trypanosome telomeres. EMBO J. 20: 579-588.
120. Myung, K., He, D.M., Lee, S.E., and Hendrickson, E.A. 1997. KARP-1: A novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. EMBO J. 16: 3172-3184.
121. Myung, K., Ghosh, G., Fattah, F.J., Li, G., Kim, H., Dutia, A., Pak, E., Smith, S., and Hendrickson, E.A. 2004. Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86. Mol. Cell. Biol. 24:5050-5059.
122. Naito, T., Matsuura, A., and Ishikawa, F. 1998. Circular chromosome formation in a fission yeast mutant defective in two ATM homologues. Nat. Genet. 20: 203-206.
123. Nakamura, T.M., Cooper, J.P., and Cech, T.R. 1998. Two modes of survival of fission yeast without telomerase. Science 282: 493-496.
124. Nakamura, T.M., Moser, B.A., and Russell, P. 2002. Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres. Genetics 161: 1437-1452.
125. Nautiyal, S., DeRisi, J.L., and Blackburn, E.H. 2002. The genome-wide expression response to telomerase deletion in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. 99: 9316-9321.
126. Neumann, A.A. and Reddel, R.R. 2002. Telomere maintenance and cancer-Look, no telomerase. Nat. Rev. Cancer 2: 879-884.
127. Niida, H., Shinkai, Y., Hande, M.P., Matsumoto, T., Takehara, S., Tachibana, M., Oshimura, M., Lansdorp, P.M., and Furuichi, Y. 2000. Telomere maintenance in telomerase-deficient mouse embryonic stem cells: Characterization of an amplified telomeric DNA. Mol. Cell. Biol. 20: 4115-4127.
128. Nugent, C.I., Bosco, G., Ross, L.O., Evans, S.K., Salinger, A.P., Moore, J.K., Haber, J.E., and Lundblad, V. 1998. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr. Biol. 8: 657-660.
129. Nussenzweig, A. 2004. H2AX: The histone guardian of the genome. DNA Repair (Amst.) (in press).
130. Parenteau, J. and Wellinger, R.J. 2002. Differential processing of leading- and lagging-strand ends at Saccharomyces cerevisiae telomeres revealed by the absence of Rad27p nuclease. Genetics 162: 1583-1594.
131. Pellicioli, A., Lee, S.B., Lucca, C., Foiani, M., and Haber, J.E. 2001. Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol. Cell 7: 293-300.
132. Pennock, E., Buckley, K., and Lundblad, V. 2001. Cdc13 delivers separate complexes to the telomere for end protection and replication. Cell 104: 387-396.
133. Peterson, S.E., Stellwagen, A.E., Diede, S.J., Singer, M.S., Haimberger, Z.W., Johnson, C.O., Tzoneva, M., and Gottschling, D.E. 2001. The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku. Nat. Genet. 27: 64-67.
134. Polotnianka, R.M., Li, J., and Lustig, A.J. 1998. The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities. Curr. Biol. 8: 831-834.
135. Porter, S.E., Greenwell, P.W., Ritchie, K.B., and Petes, T.D. 1996. The DNA-binding protein Hdf1p (a putative Ku homolog) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res. 24: 582-585.
136. Ranganathan, V., Heine, W.F., Ciccone, D.N., Rudolph, K.L., Wu, X., Chang, S., Hai, H., Ahearn, I.M., Livingston, D.M., Resnick, I., et al. 2001. Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit. Curr. Biol. 11: 962-966.
137. Ray, A. and Runge, K.W. 1999. Varying the number of telomere-bound proteins does not alter telomere length in tel1Δ cells. Proc. Natl. Acad. Sci. 96: 15044-15049.
138. Reichenbach, P., Höss, M., Azzalin, C.M., Nabholz, M., Bucher, P., and Lingner, J. 2003. A human homolog of yeast est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr. Biol. 13: 568-574.
139. Rich, T., Allen, R.L., and Wyllie, A.H. 2000. Defying death after DNA damage. Nature 407: 777-783.
140. Riha, K. and Shippen, D.E. 2003. Ku is required for telomeric C-rich strand maintenance but not for end-to-end chromosome fusions in Arabidopsis. Proc. Natl. Acad. Sci. 100: 611-615.
141. Riha, K., McKnight, T.D., Griffing, L.R., and Shippen, D.E. 2001. Living with genome instability: Plant responses to telomere dysfunction. Science 291: 1797-1800.
142. Riha, K., Watson, J.M., Parkey, J., and Shippen, D.E. 2002. Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70. EMBO J. 21: 2819-2826.
143. Ritchie, K.B. and Petes, T.D. 2000. The Mre11p/Rad50p/Xrs2p complex and the Tel1p function in a single pathway for telomere maintenance in yeast. Genetics 155: 475-479.
144. Ritchie, K.B., Mallory, J.C., and Petes, T.D. 1999. Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol. 19: 6065-6075.
145. Rouse, J. and Jackson, S.P. 2002a. Interfaces between the detection, signaling, and repair of DNA damage. Science 297: 547-551.
146. -. 2002b. Lcd1p recruits Mec1p to DNA lesions in vitro and in vivo. Mol. Cell 9: 857-869.
147. Roy, R., Meier, B., McAinsh, A.D., Feldmann, H.M., and Jackson, S.P. 2004. Separation-of-function mutants of yeast Ku80 reveal a Yku80p-Sir4p interaction involved in telomeric silencing. J. Biol. Chem. 279: 86-94.
148. Runge, K.W. and Zakian, V.A. 1996. TEL2, an essential gene required for telomere length regulation and telomere position effect in Saccharomyces cerevisiae. Mol. Cell. Biol. 16: 3094-3105.
149. Samper, E., Goytisolo, F.A., Slijepcevic, P., van Buul, P.P.W., and Blasco, M.A. 2000. Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO Rep. 1: 244-252.
150. Samper, E., Goytisolo, F.A., Ménissier-de Murcia, J., González-Suarez, E., Cigudosa, J.C., de Murcia, G., and Blasco, M.A. 2001. Normal telomere length and chromosomal end capping in poly(ADP-ribose) polymerase-deficient mice and primary cells despite increased chromosomal instability. J. Cell Biol. 154: 49-60.
151. Scherthan, H. 2001. A bouquet makes ends meet. Nat. Rev. Mol. Cell. Biol. 2: 621-627.
152. Schmitt, C.A. 2003. Senescence, apoptosis and therapy-Cutting the lifelines of cancer. Nat. Rev. Cancer 3: 286-295.
153. Schramke, V., Luciano, P., Brevet, V., Guillot, S., Corda, Y., Longhese, M.P., Gilson, E., and Geli, V. 2004. RPA regulates telomerase action by providing Est1p access to chromosome ends. Nat. Genet. 36: 46-54.
154. Schultz, N., Lopez, E., Saleh-Gohari, N., and Helleday, T. 2003. Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination. Nucleic Acids Res. 31: 4959-4964.
155. Shiloh, Y. 2003. ATM and related protein kinases: Safeguarding genome integrity. Nat. Rev. Cancer 3: 155-168.
156. Shiomi, Y., Shinozaki, A., Nakada, D., Sugimoto, K., Usukura, J., Obuse, C., and Tsurimoto, T. 2002. Clamp and clamp loader structures of the human checkpoint protein complexes, Rad9-1-1 and Rad17-RFC. Genes Cells 7: 861-868.
157. Silverman, J., Takai, H., Buonomo, S.B.C., 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. (in press).
158. Smith, G.C.M. and Jackson, S.P. 1999. The DNA-dependent protein kinase. Genes & Dev. 13: 916-934.
159. Smith, J., Zou, H., and Rothstein, R. 2000. Characterization of genetic interactions with RFA1: The role of RPA in DNA replication and telomere maintenance. Biochimie 82: 71-78.
160. 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.
161. Smolikov, S., Mazor, Y., and Krauskopf, A. 2004. ELG1, a regulator of genome stability, has a role in telomere length regulation and in silencing. Proc. Natl. Acad. Sci. 101: 1656-1661.
162. Snow, B.E., Erdmann, N., Cruickshank, J., Goldman, H., Gill R.M., Robinson, M.O., and Harrington, L. 2003. Functional conservation of the telomerase protein est1p in humans. Curr. Biol. 13: 698-704.
163. Song, K., Jung, D., Jung, Y., Lee, S.-G., and Lee, I. 2000. Interaction of human Ku70 with TRF2. FEBS Lett. 481: 81-85.
164. 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: 5532-5540.
165. Stavenhagen, J.B. and Zakian, V.A. 1998. Yeast telomeres exert a position effect on recombination between internal tracts of yeast telomeric DNA. Genes & Dev. 12: 3044-3058.
166. Stellwagen, A.E., Haimberger, Z.W., Veatch, J.R., and Gottschling, D.E. 2003. Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends. Genes & Dev. 17: 2384-2395.
167. Stucki, M. and Jackson, S.P. 2004. MDC1/NFBD1: A key regulator of the DNA damage response in higher eukaryotes. DNA Repair (Amst.) (in press).
168. Sung, P., Krejci, L., Van Komen, S., and Sehorn, M.G. 2003. Rad51 recombinase and recombination mediators. J. Biol. Chem. 278: 42729-42732.
169. Takai, H., Smogorzewska, A., and de Lange, T. 2003. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13: 1549-1556.
170. Takata, H., Kanoh, Y., Gunge, N., Shirahige, K., and Matsuura, A. 2004. Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo. Mol. Cell 14: 515-522.
171. 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.
172. Teng, S.C. and Zakian, V.A. 1999. Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Mol. Cell. Biol. 19: 8083-8093.
173. Teng, S.C., Chang, J., McCowan, B., and Zakian, V.A. 2000. Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. Mol. Cell 6: 947-952.
174. Teo, S.-H. and Jackson, S.P. 1997. Identification of Saccharomyces cerevisiae DNA ligase IV: Involvement in DNA double-strand break repair. EMBO J. 16: 4788-4795.
175. Tong, W.-M., Hande, M.P., Lansdorp, P.M., and Wang, Z.-Q. 2001. DNA strand break-sensing molecule poly(ADP-ribose) polymerase cooperates with p53 in telomere function, chromosome stability, and tumor suppression. Mol. Cell. Biol. 21: 4046-4054.
176. Tsai, Y.-L., Tseng, S.-F., Chang, S.-H., Lin, C.-C., and Teng, S.-C. 2002. Involvement of replicative polymerases, Tel1p, Mec1p, Cdc13p, and the Ku complex in telomere-telomere recombination. Mol. Cell. Biol. 22: 5679-5687.
177. Tsukamoto, Y., Kato, J., and Ikeda, H. 1997. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature 388: 900-903.
178. Tsukamoto, Y., Taggart, A.K.P., and Zakian, V.A. 2001. The role of the Mre11-Rad50-Xrs2 complex in telomerase-mediated lengthening of Saccharomyces cerevisiae telomeres. Curr. Biol. 11: 1328-1335.
179. + gene involved in DNA repair and telomere maintenance. Mol. Cell. Biol. 23: 6553-6563.
180. Unsal-Kacmaz, K. and Sancar A. 2004. Quaternary structure of ATR and effects of ATRIP and replication protein A on its DNA binding and kinase activities. Mol. Cell. Biol. 24: 1292-1300.
181. Usui, T., Ogawa, H., and Petrini, J.H.J. 2001. A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7: 1255-1266.
182. Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., and Shiloh, Y. 2003. Requirement of the MRN complex for ATM activation by DNA damage. Embo J. 22: 5612-5621.
183. van Steensel, B., Smogorzewska, A., and de Lange, T. 1998. TRF2 protects human telomeres from end-to-end fusions. Cell 92: 401-413.
184. Varley, H., Pickett, H.A., Foxon, J.L., Reddel, R.R., and Royle, N.J. 2002. Molecular characterization of inter-telomere and intra-telomere mutations in human ALT cells. Nat. Genet. 30: 301-305.
185. Viscardi, V., Baroni, E., Romano, M., Lucchini, G., and Longhese, M.P. 2003. Sudden telomere lengthening triggers a Rad53-dependent checkpoint in Saccharomyces cerevisiae. Mol. Biol. Cell 14: 3126-3143.
186. von Zglinicki, T. 2002. Oxidative stress shortens telomeres. Trends Biochem. Sci. 27: 339-344.
187. Wei, C., Skopp, R., Takata, M., Takeda, S., and Price, C.M. 2002. Effects of double-strand break repair proteins on vertebrate telomere structure. Nucleic Acids Res. 30: 2862-2870.
188. Weizman, N., Shiloh, Y., and Barzilai, A. 2003. Contribution of the Atm protein to maintaining cellular homeostasis evidenced by continuous activation of the AP-1 pathway in Atm-deficient brains. J. Biol. Chem. 278: 6741-6747.
189. Wilson, S., Warr, N., Taylor, D.L., and Watts, F.Z. 1999. The role of Schizosaccharomyces pombe Rad32, the Mre11 homologue, and other DNA damage response proteins in non-homologous end joining and telomere length maintenance. Nucleic Acids Res. 27: 2655-2661.
190. Wong, K.-K., Chang, S., Weiler, S.R., Ganesan, S., Chaudhuri, J., Zhu, C., Artandi, S.E., Rudolph, K.L., Gottlieb, G.J., Chin, L., et al. 2000. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat. Genet. 26: 85-88.
191. Wong, J.M., Kusdra, L., and Collins, K. 2002. Subnuclear shuttling of human telomerase induced by transformation and DNA damage. Nat. Cell. Biol. 4: 731-736.
192. Zhou, B.-B.S. and Elledge, S.J. 2000. The DNA damage response: Putting checkpoints in perspective. Nature 408: 433-439.
193. Zhu, X.-D., Küster, B., Mann, M., Petrini, J.H.J., and Lange, T.D. 2000. Cell-cycle-regulated association of RAD50/MRE11/ NBS1 with TRF2 and human telomeres. Nat. Genet. 25: 347-352.
194. Zhu, X.D., Niedemhofer, 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.
195. Zou, L. and Elledge, S.J. 2003. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300: 1542-1548.