Regulation of the cellular DNA double-strand break response

Biochemistry and Cell Biology

Volumn 85, Issue 6, 2007, Pages 663-674

  Cann, Kendra L ^a   Hicks, Geoffrey G ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Apoptosis; Cell cycle checkpoints; DNA double strand breaks; DNA repair; Gamma radiation

Indexed keywords

CELL DEATH; ENZYME ACTIVITY; GAMMA RAYS; MAMMALS;

CELL CYCLE CHECKPOINTS; DNA REPAIR;

DNA;

ATM PROTEIN; ATR PROTEIN; DOUBLE STRANDED DNA;

ANIMAL CELL; APOPTOSIS; CELL CYCLE G1 PHASE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE REGULATION; CELL CYCLE S PHASE; CONTROLLED STUDY; DNA DAMAGE; DNA REPAIR; DNA REPLICATION; DOUBLE STRANDED DNA BREAK; HOMOLOGOUS RECOMBINATION; IONIZING RADIATION; MAMMAL CELL; NONHUMAN; REVIEW;

ANIMALS; APOPTOSIS; CELL CYCLE; CELL CYCLE PROTEINS; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; DNA-BINDING PROTEINS; HUMANS; PROTEIN-SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS;

MAMMALIA;

EID: 38849129888     PISSN: 08298211     EISSN: None     Source Type: Journal    
DOI: 10.1139/O07-135     Document Type: Review

References (118)

1. Adair, G.M., Rolig, R.L., Moore-Faver, D., Zabelshansky, M., Wilson, J.H., and Nairn, R.S. 2000. Role of ERCC1 in removal of long non-homologous tails during targeted homologous recombination. EMBO J. 19: 5552-5561. doi:10.1093/emboj/19.20.5552.
2. Agami, R., and Bernards, R. 2000. Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage. Cell, 102: 55-66. doi:10.1016/S0092-8674(00)00010-6.
3. Anderson, L., Henderson, C., and Adachi, Y. 2001. Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage. Mol. Cell. Biol. 21: 1719-1729. doi:10.1128/MCB.21.5.1719-1729.2001.
4. Andreassen, P.R., Ho, G.P., and D'Andrea, A.D. 2006. DNA damage responses and their many interactions with the replication fork. Carcinogenesis, 27: 883-892. doi:10.1093/carcin/bgi319.
5. Bakkenist, C.J., and Kastan, M.B. 2003. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature, 421: 499-506. doi:10.1038/nature01368.
6. Barlow, C., Hirotsune, S., Paylor, R., Liyanage, M., Eckhaus, M., Collins, F., et al. 1996. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell, 86: 159-171. doi:10.1016/S0092-8674(00)80086-0.
7. Bartek, J., and Lukas, J. 2001a. Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr. Opin. Cell Biol. 13: 738-747. doi:10.1016/S0955-0674(00)00280-5.
8. Bartek, J., and Lukas, J. 2001b. Pathways governing G1/S transition and their response to DNA damage. FEBS Lett. 490: 117-122. doi:10.1016/S0014-5793(01)02114-7.
9. Bartek, J., Lukas, C., and Lukas, J. 2004. Checking on DNA damage in S phase. Nat. Rev. Mol. Cell Biol. 5: 792-804. doi:10.1038/nrm1493.
10. Baskaran, R., Wood, L.D., Whitaker, L.L., Canman, C.E., Morgan, S.E., Xu, Y., et al. 1997. Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature, 387: 516-519. doi:10.1038/387516a0.
11. Bernstein, C., Bernstein, H., Payne, C.M., and Garewal, H. 2002. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat. Res. 511: 145-178. doi:10.1016/S1383-5742(02)00009-1.
12. Borner, C. 2003. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol. Immunol. 39: 615-647. doi:10.1016/S0161- 5890(02)00252-3.
13. Bree, R.T., Neary, C., Samali, A., and Lowndes, N.F. 2004. The switch from survival responses to apoptosis after chromosomal breaks. DNA Repair (Amst.), 3: 989-995. doi:10.1016/j.dnarep.2004.03.016.
14. Burma, S., Chen, B.P., Murphy, M., Kurimasa, A., and Chen, D.J. 2001. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem. 276: 42462-42467. doi:10.1074/jbc.C100466200.
15. Cann, K.L., and Hicks, G.G. 2006. Absence of an immediate G1/S checkpoint in primary MEFs following gamma-irradiation identifies a novel checkpoint switch. Cell Cycle, 5: 1823-1830.
16. Cazzalini, O., Perucca, P., Riva, F., Stivala, L.A., Bianchi, L., Vannini, V., Ducommun, B., and Prosperi, E. 2003. p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase delta at the G1/S phase transition. Cell Cycle, 2: 596-603.
17. Celeste, A., Petersen, S., Romanienko, P.J., Fernandez-Capetillo, O., Chen, H.T., Sedelnikova, O.A., et al. 2002. Genomic instability in mice lacking histone H2AX. Science, 296: 922-927. doi:10.1126/science.1069398.
18. Celeste, A., Fernandez-Capetillo, O., Kruhlak, M.J., Pilch, D.R., Staudt, D.W., Lee, A., et al. 2003. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat. Cell Biol. 5: 675-679. doi:10.1038/ncb1004.
19. Chan, T.A., Hermeking, H., Lengauer, C., Kinzler, K.W., and Vogelstein, B. 1999. 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature, 401: 616-620. doi:10.1038/44188.
20. Chen, G., Yuan, S.S., Liu, W., Xu, Y., Trujillo, K., Song, B., et al. 1999. Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. J. Biol. Chem. 274: 12748-12752. doi:10.1074/jbc.274.18.12748.
21. Chen, M.S., Ryan, C.E., and Piwnica-Worms, H. 2003. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol. Cell. Biol. 23: 7488-7497. doi:10.1128/MCB.23.21.7488-7497. 2003.
22. Chen, C., Shimizu, S., Tsujimoto, Y., and Motoyama, N. 2005. Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage. Biochem. Biophys. Res. Commun. 333: 427-431. doi:10.1016/j.bbrc. 2005.05.126.
23. Cortez, D., Guntuku, S., Qin, J., and Elledge, S.J. 2001. ATR and ATRIP: partners in checkpoint signaling. Science, 294: 1713-1716. doi:10.1126/science.1065521.
24. Costanzo, V., Robertson, K., Ying, C.Y., Kim, E., Avvedimento, E., Gottesman, M., Grieco, D., and Gautier, J. 2000. Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage. Mol. Cell, 6: 649-659. doi:10.1016/S1097-2765(00)00063-0.
25. Cuadrado, M., Martinez-Pastor, B., Murga, M., Toledo, L.I., Gutierrez-Martinez, P., Lopez, E., and Fernandez-Capetillo, O. 2006. ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J. Exp. Med. 203: 297-303. doi:10.1084/jem.20051923.
26. Dasika, G.K., Lin, S.C., Zhao, S., Sung, P., Tomkinson, A., and Lee, E.Y. 1999. DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene, 18: 7883-7899. doi:10.1038/sj.onc.1203283.
27. DeGregori, J. 2002. The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim. Biophys. Acta, 1602: 131-150.
28. Duursma, A., and Agami, R. 2005. p53-dependent regulation of Cdc6 protein stability controls cellular proliferation. Mol. Cell. Biol. 25: 6937-6947. doi:10.1128/MCB.25.16.6937-6947.2005.
29. Falck, J., Mailand, N., Syljuasen, R.G., Bartek, J., and Lukas, J. 2001. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature, 410: 842-847. doi:10.1038/35071124.
30. Falck, J., Petrini, J.H., Williams, B.R., Lukas, J., and Bartek, J. 2002. The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nat. Genet. 30: 290-294. doi:10.1038/ng845.
31. Falck, J., Coates, J., and Jackson, S.P. 2005. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature, 434: 605-611. doi:10.1038/nature03442.
32. Fernandez-Capetillo, O., Chen, H.T., Celeste, A., Ward, I., Romanienko, P.J., Morales, J.C., et al. 2002. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat. Cell Biol. 4: 993-997. doi:10.1038/ncb884.
33. Flores-Rozas, H., Kelman, Z., Dean, F.B., Pan, Z.Q., Harper, J.W., Elledge, S.J., O'Donnell, M., and Hurwitz, J. 1994. Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme. Proc. Natl. Acad. Sci. U.S.A. 91: 8655-8659. doi:10.1073/pnas.91.18.8655.
34. 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. doi:10.1093/emboj/cdg274.
35. Gatei, M., Young, D., Cerosaletti, K.M., Desai-Mehta, A., Spring, K., Kozlov, S., et al. 2000. ATM-dependent phosphorylation of nibrin in response to radiation exposure. Nat. Genet. 25: 115-119. doi:10.1038/75508.
36. Girard, P.M., Riballo, E., Begg, A.C., Waugh, A., and Jeggo, P.A. 2002. Nbs1 promotes ATM dependent phosphorylation events including those required for G1/S arrest. Oncogene, 21: 4191-4199. doi:10.1038/sj.onc.1205596.
37. 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. doi:10.1038/nature01445.
38. Gudmundsdottir, K., and Ashworth, A. 2006. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene, 25: 5864-5874. doi:10.1038/sj.onc.1209874.
39. Haaf, T., Golub, E.I., Reddy, G., Radding, C.M., and Ward, D.C. 1995. Nuclear foci of mammalian Rad51 recombination protein in somatic cells after DNA damage and its localization in synaptonemal complexes. Proc. Natl. Acad. Sci. U.S.A. 92: 2298-2302. doi:10.1073/pnas.92.6.2298.
40. Hiom, K. 1999. DNA repair: Rad52 - the means to an end. Curr. Biol. 9: R446-R448. doi:10.1016/S0960-9822(99)80278-4.
41. Hoeijmakers, J.H. 2001. Genome maintenance mechanisms for preventing cancer. Nature, 411: 366-374. doi:10.1038/35077232.
42. Hong, Y., and Stambrook, P.J. 2004. Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation. Proc. Natl. Acad. Sci. U.S.A. 101: 14443-14448. doi:10.1073/pnas. 0401346101.
43. Huang, Y., Nakada, S., Ishiko, T., Utsugisawa, T., Datta, R., Kharbanda, S., et al. 1999. Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA damage. Mol. Cell. Biol. 19: 2986-2997.
44. Iftode, C., Daniely, Y., and Borowiec, J.A. 1999. Replication protein A (RPA): the eukaryotic SSB. Crit. Rev. Biochem. Mol. Biol. 34: 141-180. doi:10.1080/10409239991209255.
45. Jackson, S.P. 2001. Detecting, signalling and repairing DNA double-strand breaks. Biochem. Soc. Trans. 29: 655-661. doi:10.1042/BST0290655.
46. Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G.C., Lukas, J., and Jackson, S.P. 2006. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat. Cell Biol. 8: 37-45. doi:10.1038/ncb1337.
47. Jonnalagadda, V.S., Matsuguchi, T., and Engelward, B.P. 2005. Interstrand crosslink-induced homologous recombination carries an increased risk of deletions and insertions. DNA Repair (Amst.), 4: 594-605. doi:10.1016/j.dnarep.2005.02.002.
48. Karagiannis, T.C., and El-Osta, A. 2004. Double-strand breaks: signaling pathways and repair mechanisms. Cell. Mol. Life Sci. 61: 2137-2147. doi:10.1007/s00018-004-4174-0.
49. Karlsson, A., Deb-Basu, D., Cherry, A., Turner, S., Ford, J., and Felsher, D.W. 2003. Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression. Proc. Natl. Acad. Sci. U.S.A. 100: 9974-9979. doi:10.1073/pnas.1732638100.
50. Kastan, M.B., and Bartek, J. 2004. Cell-cycle checkpoints and cancer. Nature, 432: 316-323. doi:10.1038/nature03097.
51. Kastan, M.B., Onyekwere, O., Sidransky, D., Vogelstein, B., and Craig, R.W. 1991. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51: 6304-6311.
52. Khanna, K.K., and Jackson, S.P. 2001. DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 27: 247-254. doi:10.1038/85798.
53. Khosravi, R., Maya, R., Gottlieb, T., Oren, M., Shiloh, Y., and Shkedy, D. 1999. Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc. Natl. Acad. Sci. U.S.A. 96: 14973-14977. doi:10.1073/pnas.96.26.14973.
54. Kozlov, S.V., Graham, M.E., Peng, C., Chen, P., Robinson, P.J., and Lavin, M.F. 2006. Involvement of novel autophosphorylation sites in ATM activation. EMBO J. 25: 3504-3514. doi:10.1038/sj.emboj.7601231.
55. Kuerbitz, S.J., Plunkett, B.S., Walsh, W.V., and Kastan, M.B. 1992. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc. Natl. Acad. Sci. U.S.A. 89: 7491-7495. doi:10.1073/pnas.89.16.7491.
56. Kurz, E.U., and Lees-Miller, S.P. 2004. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst.), 3: 889-900. doi:10.1016/j.dnarep.2004.03.029.
57. Larner, J.M., Lee, H., Little, R.D., Dijkwel, P.A., Schildkraut, C.L., and Hamlin, J.L. 1999. Radiation down-regulates replication origin activity throughout the S phase in mammalian cells. Nucleic Acids Res. 27: 803-809. doi:10.1093/nar/27.3.803.
58. Lee, J.H., and Paull, T.T. 2005. ATM activation by DNA doublestrand breaks through the Mre11-Rad50-Nbs1 complex. Science, 308: 551-554. doi:10.1126/science.1108297.
59. Li, L., and Zou, L. 2005. Sensing, signaling, and responding to DNA damage: organization of the checkpoint pathways in mammalian cells. J. Cell. Biochem. 94: 298-306. doi:10.1002/jcb.20355.
60. Lim, D.S., Kim, S.T., Xu, B., Maser, R.S., Lin, J., Petrini, J.H., and Kastan, M.B. 2000. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature, 404: 613-617. doi:10.1038/35007091.
61. Liu, Y., Li, M., Lee, E.Y., and Maizels, N. 1999. Localization and dynamic relocalization of mammalian Rad52 during the cell cycle and in response to DNA damage. Curr. Biol. 9: 975-978. doi:10.1016/S0960-9822(99)80427-8.
62. Lou, Z., Minter-Dykhouse, K., Wu, X., and Chen, J. 2003. MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Nature, 421: 957-961. doi:10.1038/nature01447.
63. Lou, Z., Minter-Dykhouse, K., Franco, S., Gostissa, M., Rivera, M.A., Celeste, A., et al. 2006. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell, 21: 187-200. doi:10.1016/j.molcel.2005.11.025.
64. Lowe, S.W., Schmitt, E.M., Smith, S.W., Osborne, B.A., and Jacks, T. 1993. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature, 362: 847-849. doi:10.1038/362847a0.
65. Mailand, N., and Diffley, J.F. 2005. CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell, 122: 915-926. doi:10.1016/j.cell.2005.08.013.
66. Mailand, N., Falck, J., Lukas, C., Syljuasen, R.G., Welcker, M., Bartek, J., and Lukas, J. 2000. Rapid destruction of human Cdc25A in response to DNA damage. Science, 288: 1425-1429. doi:10.1126/science.288.5470.1425.
67. Marheineke, K., and Hyrien, O. 2004. Control of replication origin density and firing time in Xenopus egg extracts: role of a caffeine-sensitive, ATR-dependent checkpoint. J. Biol. Chem. 279: 28071-28081. doi:10.1074/jbc.M401574200.
68. Matsui, Y., Tsuchida, Y., and Keng, P.C. 2001. Effects of p53 mutations on cellular sensitivity to ionizing radiation. Am. J. Clin. Oncol. 24: 486-490. doi:10.1097/00000421-200110000-00014.
69. Maya, R., Balass, M., Kim, S.T., Shkedy, D., Leal, J.F., Shifman, O., et al. 2001. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev. 15: 1067-1077. doi:10.1101/gad. 886901.
70. Miao, H., Seiler, J.A., and Burhans, W.C. 2003. Regulation of cellular and SV40 virus origins of replication by Chk1-dependent intrinsic and UVC radiation-induced checkpoints. J. Biol. Chem. 278: 4295-4304. doi:10.1074/jbc.M204264200.
71. Mochan, T.A., Venere, M., DiTullio, R.A., Jr., and Halazonetis, T.D. 2003. 53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage. Cancer Res. 63: 8586-8591.
72. Myers, J.S., and Cortez, D. 2006. Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J. Biol. Chem. 281: 9346-9350. doi:10.1074/jbc.M513265200.
73. Niida, H., and Nakanishi, M. 2006. DNA damage checkpoints in mammals. Mutagenesis, 21: 3-9. doi:10.1093/mutage/gei063.
74. Obaya, A.J., and Sedivy, J.M. 2002. Regulation of cyclin-Cdk activity in mammalian cells. Cell. Mol. Life Sci. 59: 126-142. doi:10.1007/s00018- 002-8410-1.
75. O'Keefe, R.T., Henderson, S.C., and Spector, D.L. 1992. Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences. J. Cell Biol. 116: 1095-1110. doi:10.1083/jcb.116.5.1095.
76. Painter, R.B., and Young, B.R. 1980. Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc. Natl. Acad. Sci. U.S.A. 77: 7315-7317. doi:10.1073/pnas.77.12.7315.
77. Paull, T.T., and Lee, J.H. 2005. The Mre11/Rad50/Nbs1 complex and its role as a DNA double-strand break sensor for ATM. Cell Cycle, 4: 737-740.
78. Pellegrini, L., and Venkitaraman, A. 2004. Emerging functions of BRCA2 in DNA recombination. Trends Biochem. Sci. 29: 310-316. doi:10.1016/j.tibs.2004.04.009.
79. Pellegrini, M., Celeste, A., Difilippantonio, S., Guo, R., Wang, W., Feigenbaum, L., and Nussenzweig, A. 2006. Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo. Nature, 443: 222-225. doi:10.1038/nature05112.
80. Povirk, L.F. 1996. DNA damage and mutagenesis by radiomimetic DNA-cleaving agents: bleomycin, neocarzinostatin and other enediynes. Mutat. Res. 355: 71-89.
81. Rogakou, E.P., Pilch, D.R., Orr, A.H., Ivanova, V.S., and Bonner, W.M. 1998. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273: 5858-5868. doi:10.1074/jbc.273.10.5858.
82. Rogakou, E.P., Boon, C., Redon, C., and Bonner, W.M. 1999. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J. Cell Biol. 146: 905-916. doi:10.1083/jcb.146.5.905.
83. Sancar, A., Lindsey-Boltz, L.A., Unsal-Kacmaz, K., and Linn, S. 2004. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73: 39-85. doi:10.1146/annurev.biochem.73.011303. 073723.
84. Sargent, R.G., Meservy, J.L., Perkins, B.D., Kilburn, A.E., Intody, Z., Adair, G.M., Nairn, R.S., and Wilson, J.H. 2000. Role of the nucleotide excision repair gene ERCC1 in formation of recombination-dependent rearrangements in mammalian cells. Nucleic Acids Res. 28: 3771-3778. doi:10.1093/nar/28.19. 3771.
85. Schafer, K.A. 1998. The cell cycle: a review. Vet. Pathol. 35: 461-478.
86. Schuler, M., and Green, D.R. 2005. Transcription, apoptosis and p53: catch-22. Trends Genet. 21: 182-187. doi:10.1016/j.tig.2005.01.001.
87. Schultz, L.B., Chehab, N.H., Malikzay, A., and Halazonetis, T.D. 2000. p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J. Cell Biol. 151: 1381-1390. doi:10.1083/jcb.151.7.1381.
88. Shechter, D., Costanzo, V., and Gautier, J. 2004. ATR and ATM regulate the timing of DNA replication origin firing. Nat. Cell Biol. 6: 648-655. doi:10.1038/ncb1145.
89. Shimura, T., Toyoshima, M., Adiga, S.K., Kunoh, T., Nagai, H., Shimizu, N., Inoue, M., and Niwa, O. 2006. Suppression of replication fork progression in low-dose-specific p53-dependent Sphase DNA damage checkpoint. Oncogene, 25: 5921-5932. doi:10.1038/sj.onc.1209624.
90. Sionov, R.V., and Haupt, Y. 1999. The cellular response to p53: the decision between life and death. Oncogene, 18: 6145-6157. doi:10.1038/sj.onc.1203130.
91. Sorensen, C.S., Syljuasen, R.G., Lukas, J., and Bartek, J. 2004. ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage. Cell Cycle, 3: 941-945.
92. Stark, G.R., and Taylor, W.R. 2004. Analyzing the G2/M checkpoint. Methods Mol. Biol. 280: 51-82.
93. Stark, J.M., Pierce, A.J., Oh, J., Pastink, A., and Jasin, M. 2004. Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol. Cell. Biol. 24: 9305-9316. doi:10.1128/MCB.24.21.9305- 9316.2004.
94. Stewart, G.S., Wang, B., Bignell, C.R., Taylor, A.M., and Elledge, S.J. 2003. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature, 421: 961-966. doi:10.1038/nature01446.
95. Takai, H., Naka, K., Okada, Y., Watanabe, M., Harada, N., Saito, S., et al. 2002. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J. 21: 5195-5205. doi:10.1093/emboj/cdf506.
96. Tan, T.L., Essers, J., Citterio, E., Swagemakers, S.M., de Wit, J., Benson, F.E., Hoeijmakers, J.H., and Kanaar, R. 1999. Mouse Rad54 affects DNA conformation and DNA-damage-induced Rad51 foci formation. Curr. Biol. 9: 325-328. doi:10.1016/S0960-9822(99)80142-0.
97. Thacker, J. 2005. The RAD51 gene family, genetic instability and cancer. Cancer Lett. 219: 125-135. doi:10.1016/j.canlet.2004.08.018.
98. Tsukamoto, Y., and Ikeda, H. 1998. Double-strand break repair mediated by DNA end-joining. Genes Cells, 3: 135-144. doi:10.1046/j.1365-2443.1998. 00180.x.
99. Uto, K., Inoue, D., Shimuta, K., Nakajo, N., and Sagata, N. 2004. Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism. EMBO J. 23: 3386-3396. doi:10.1038/sj.emboj.7600328.
100. van den Bosch, M., Bree, R.T., and Lowndes, N.F. 2003. The MRN complex: coordinating and mediating the response to broken chromosomes. EMBO Rep. 4: 844-849. doi:10.1038/sj.embor.embor925.
101. Vilenchik, M.M., and Knudson, A.G. 2003. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc. Natl. Acad. Sci. U.S.A. 100: 12871-12876. doi:10.1073/pnas.2135498100.
102. Waga, S., Hannon, G.J., Beach, D., and Stillman, B. 1994. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature, 369: 574-578. doi:10.1038/369574a0.
103. Ward, I.M., and Chen, J. 2001. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J. Biol. Chem. 276: 47759-47762. doi:10.1074/jbc.M009785200.
104. Westphal, C.H., Rowan, S., Schmaltz, C., Elson, A., Fisher, D.E., and Leder, P. 1997. atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in resistance to acute radiation toxicity. Nat. Genet. 16: 397-401. doi:10.1038/ng0897-397.
105. Williams, R.S., Bernstein, N., Lee, M.S., Rakovszky, M.L., Cui, D., Green, R., Weinfeld, M., and Glover, J.N. 2005. Structural basis for phosphorylation-dependent signaling in the DNA-damage response. Biochem. Cell Biol. 83: 721-727. doi:10.1139/o05-153.
106. Xiong, Y., Hannon, G.J., Zhang, H., Casso, D., Kobayashi, R., and Beach, D. 1993. p21 is a universal inhibitor of cyclin kinases. Nature, 366: 701-704. doi:10.1038/366701a0.
107. Xu, Y., and Baltimore, D. 1996. Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev. 10: 2401-2410. doi:10.1101/gad.10.19.2401.
108. Xu, B., and Kastan, M.B. 2004. Analyzing cell cycle checkpoints after ionizing radiation. Methods Mol. Biol. 281: 283-292.
109. Xu, B., Kim, S., and Kastan, M.B. 2001. Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol. Cell. Biol. 21: 3445-3450. doi:10.1128/MCB.21.10.3445-3450.2001.
110. Xu, B., Kim, S.T., Lim, D.S., and Kastan, M.B. 2002a. Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation. Mol. Cell. Biol. 22: 1049-1059. doi:10.1128/MCB.22.4.1049-1059.2002.
111. Xu, B., O'Donnell, A.H., Kim, S.T., and Kastan, M.B. 2002b. Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer Res. 62: 4588-4591.
112. Yoshida, K., and Miki, Y. 2004. Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci. 95: 866-871. doi:10.1111/j.1349-7006.2004.tb02195.x.
113. Yuan, Z.M., Huang, Y., Ishiko, T., Nakada, S., Utsugisawa, T., Kharbanda, S., et al. 1998. Regulation of Rad51 function by c-Abl in response to DNA damage. J. Biol. Chem. 273: 3799-3802. doi:10.1074/jbc.273.7.3799.
114. Yuan, S.S., Chang, H.L., and Lee, E.Y. 2003. Ionizing radiation-induced Rad51 nuclear focus formation is cell cycle-regulated and defective in both ATM(-/-) and c-Abl(-/-) cells. Mutat. Res. 525: 85-92.
115. Zhang, J., Willers, H., Feng, Z., Ghosh, J.C., Kim, S., Weaver, D.T., et al. 2004. Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair. Mol. Cell. Biol. 24: 708-718. doi:10.1128/MCB.24.2.708-718.2004.
116. Zhang, J., Ma, Z., Treszezamsky, A., and Powell, S.N. 2005. MDC1 interacts with Rad51 and facilitates homologous recombination. Nat. Struct. Mol. Biol. 12: 902-909. doi:10.1038/nsmb991.
117. Zhao, H., Watkins, J.L., and Piwnica-Worms, H. 2002. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc. Natl. Acad. Sci. U.S.A. 99: 14795-14800. doi:10.1073/pnas.182557299.
118. Zou, L., and Elledge, S.J. 2003. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science, 300: 1542-1548. doi:10.1126/science.1083430.