DNA damage sensing by the ATM and ATR kinases

Cold Spring Harbor Perspectives in Biology

Volumn 5, Issue 9, 2013, Pages

  Maréchal, Alexandre ^a   Zou, Lee ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; ATR PROTEIN, HUMAN;

ARTICLE; CHEMICAL STRUCTURE; CHROMATIN; DNA DAMAGE; GENETICS; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ATAXIA TELANGIECTASIA MUTATED PROTEINS; CHROMATIN; DNA DAMAGE; MODELS, MOLECULAR; RECEPTOR CROSS-TALK; SIGNAL TRANSDUCTION;

EID: 84870757506     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a012716     Document Type: Article

References (154)

1. Adams K. E, Medhurst AL, Dart DA, Lakin ND. 2006. Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex. Oncogene 25: 3894-3904.
2. Adamson B., Smogorzewska A, Sigoillot FD, King RW, Elledge SJ. 2012. A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response. Nat Cell Biol 14: 318-328.
3. Ayoub N., Jeyasekharan AD, Bernal JA, Venkitaraman AR. 2008. HP1-b mobilization promotes chromatin changes that initiate theDNAdamage response. Nature 453: 682-686.
4. Bakkenist C. J, KastanMB. 2003. DNAdamage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499-506.
5. Ball H. L, Cortez D. 2005. ATRIP oligomerization is required for ATR-dependent checkpoint signaling. J Biol Chem 280: 31390-31396.
6. Ball H. L, Myers JS, Cortez D. 2005. ATRIP binding to replication protein A-single-stranded DNA promotes ATRATRIP localization but is dispensable for Chk1 phosphorylation. Mol Biol Cell 16: 2372-2381.
7. Balmus G., Zhu M, Mukherjee S, Lyndaker AM, Hume KR, Lee J., Riccio ML, Reeves AP, Sutter NB, Noden DM, et al. 2012. Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1. Hum Mol Genet 21: 3408-3420.
8. Bekker-Jensen S, Rendtlew Danielsen J, Fugger K, Gromova I, Nerstedt A, Lukas C, Bartek J, Lukas J, Mailand N. 2010. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat Cell Biol 12: 80-86.
9. Beli P., Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L., Mann M, Jackson SP, Choudhary C. 2012. Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response. Mol Cell 46: 212-225.
10. Bensimon A., Schmidt A, Ziv Y, Elkon R, Wang SY, Chen DJ, Aebersold R., Shiloh Y. 2010. ATM-dependent and-independent dynamics of the nuclear phosphoproteome after DNA damage. Sci Signal 3: rs3.
11. Berkovich E, Monnat RJ Jr, Kastan MB. 2007. Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol 9: 683-690.
12. Bolderson E., Tomimatsu N, Richard DJ, Boucher D, Kumar R, Pandita TK, Burma S, Khanna KK. 2010. Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks. Nucleic Acids Res 38: 1821-1831.
13. Bolderson E., Savage KI, Mahen R, Pisupati V, Graham ME, Richard D. J, Robinson PJ, Venkitaraman AR, Khanna KK. 2012. Kruppel-associated Box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1b (HP1-b) mobilization and DNA repair in heterochromatin. J Biol Chem 287: 28122-28131.
14. Bouwman P., Jonkers J. 2012. The effects of deregulatedDNA damage signalling on cancer chemotherapy response and resistance. Nat Rev Cancer 12: 587-598.
15. Brown E. J, Baltimore D. 2000. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev 14: 397-402.
16. Brown E. J, BaltimoreD. 2003. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17: 615-628.
17. Buis J, Wu Y, Deng Y, Leddon J, Westfield G, Eckersdorff M, Sekiguchi J. M, Chang S, Ferguson DO. 2008. Mre11 nuclease activity has essential roles in DNA repair and genomic stability distinct from ATM activation. Cell 135: 85-96.
18. Bunting S. F, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A., Feldhahn N, Fernandez-Capetillo O, Cao L, et al. 2010. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141: 243-254.
19. Byun T. S, Pacek M, Yee MC, Walter JC, Cimprich KA. 2005. Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev 19: 1040-1052.
20. Casper A. M, Nghiem P, Arlt MF, Glover TW. 2002. ATR regulates fragile site stability. Cell 111: 779-789.
21. Chanoux R. A, Yin B, Urtishak KA, Asare A, Bassing CH, Brown E.J. 2009. ATR and H2AX cooperate in maintaining genome stability under replication stress. J Biol Chem 284: 5994-6003.
22. Chapman J. R, Jackson SP. 2008. Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage. EMBO Rep 9: 795-801.
23. Charrier J. D, Durrant SJ, Golec JM, Kay DP, Knegtel RM, MacCormick S, Mortimore M, O'Donnell ME, Pinder JL, Reaper P. M, et al. 2011. Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J Med Chem 54: 2320-2330.
24. Ciccia A., Elledge SJ. 2010. TheDNAdamage response:Making it safe to play with knives. Mol Cell 40: 179-204.
25. Cimprich K. A, CortezD. 2008. ATR: An essential regulator of genome integrity. Nat Rev Mol Cell Biol 9: 616-627.
26. Cortez D., Guntuku S, Qin J, Elledge SJ. 2001. ATR and ATRIP: Partners in checkpoint signaling. Science 294: 1713-1716.
27. Cotta-Ramusino C, McDonald ER III, Hurov K, Sowa ME, Harper J. W, Elledge SJ. 2011. A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science 332: 1313-1317.
28. de Klein A, Muijtjens M, van Os R, Verhoeven Y, Smit B, Carr A. M, Lehmann AR, Hoeijmakers JH. 2000. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr Biol 10: 479-482.
29. Delacroix S., Wagner JM, Kobayashi M, Yamamoto K, Karnitz LM. 2007. The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev 21: 1472-1477.
30. DiTullio RA Jr, Mochan TA, Venere M, Bartkova J, Sehested M, Bartek J, Halazonetis TD. 2002. 53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer. Nat Cell Biol 4: 998-1002.
31. Doil C., Mailand N, Bekker-Jensen S, Menard P, Larsen DH, Pepperkok R., Ellenberg J, Panier S, Durocher D, Bartek J, et al. 2009. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allowaccumulation of repair proteins. Cell 136: 435-446.
32. Dupre A., Boyer-Chatenet L, Gautier J. 2006. Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex. Nat Struct Mol Biol 13: 451-457.
33. Ellison V., Stillman B. 2003. Biochemical characterization of DNA damage checkpoint complexes: Clamp loader and clamp complexes with specificity for 50 recessed DNA. PLoS Biol 1: E33.
34. Fabbro M., Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA, Khanna KK. 2004. BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage. J Biol Chem 279: 31251-31258.
35. Falck J., Coates J, Jackson SP. 2005. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434: 605-611.
36. Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, Naka K, Xia Z, Camerini-Otero RD, Motoyama N, et al. 2002. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol 4: 993-997.
37. Flynn R. L, Zou L. 2011. ATR: A master conductor of cellular responses to DNA replication stress. Trends Biochem Sci 36: 133-140.
38. Furuya K., Poitelea M, Guo L, Caspari T, Carr AM. 2004. Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1. Genes Dev 18: 1154-1164.
39. Galanty Y., Belotserkovskaya R, Coates J, Polo S, Miller KM, Jackson S.P. 2009. Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 462: 935-939.
40. Goodarzi A. A, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Lobrich M, Jeggo PA. 2008. ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 31: 167-177.
41. Guo Z, Kozlov S, LavinMF, PersonMD, Paull TT. 2010. ATM activation by oxidative stress. Science 330: 517-521.
42. Halazonetis T. D, Gorgoulis VG, Bartek J. 2008. An oncogene-induced DNA damage model for cancer development. Science 319: 1352-1355.
43. Huen M. S, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J. 2007. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131: 901-914.
44. Hurov K. E, Cotta-Ramusino C, Elledge SJ. 2010. A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes Dev 24: 1939-1950.
45. Itakura E., Sawada I, Matsuura A. 2005. Dimerization of the ATRIP protein through the coiled-coil motif and its implication to the maintenance of stalled replication forks. Mol Biol Cell 16: 5551-5562.
46. Jazayeri A., Falck J, Lukas C, Bartek J, Smith GC, Lukas J, 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.
47. Jazayeri A., Balestrini A, Garner E, Haber JE, Costanzo V. 2008. Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity. EMBO J 27: 1953-1962.
48. Jungmichel S., Clapperton JA, Lloyd J, Hari FJ, Spycher C, Pavic L., Li J, Haire LF, Bonalli M, Larsen DH, et al. 2012. The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator. Nucleic Acids Res 40: 3913-3928.
49. Kang J., Ferguson D, Song H, Bassing C, Eckersdorff M, Alt FW, Xu Y. 2005. Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression. Mol Cell Biol 25: 661-670.
50. Kim H., Chen J, Yu X. 2007a. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316: 1202-1205.
51. Kim H, Huang J, Chen J. 2007b. CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response. Nat Struct Mol Biol 14: 710-715.
52. Kitagawa R., Bakkenist CJ, McKinnon PJ, Kastan MB. 2004. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev 18: 1423-1438.
53. Kolas N. K, Chapman JR, Nakada S, Ylanko J, Chahwan R, Sweeney F. D, Panier S, Mendez M, Wildenhain J, Thomson TM, et al. 2007. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318: 1637-1640.
54. Kousholt A. N, Fugger K, Hoffmann S, Larsen BD, Menzel T, Sartori A. A, Sorensen CS. 2012. CtIP-dependent DNA resection is required for DNA damage checkpoint maintenance but not initiation. J Cell Biol 197: 869-876.
55. Kumagai A., Lee J, Yoo HY, Dunphy WG. 2006. TopBP1 activates the ATR-ATRIP complex. Cell 124: 943-955.
56. Lavin M.F. 2008. Ataxia-telangiectasia: From a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9: 759-769.
57. Lee J., Dunphy WG. 2010. Rad17 plays a central role in establishment of the interaction between TopBP1 and the Rad9-Hus1-Rad1 complex at stalled replication forks. Mol Biol Cell 21: 926-935.
58. Lee J. H, Paull TT. 2004. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304: 93-96.
59. Lee J. H, Paull TT. 2005. ATM activation by DNA doublestrand breaks through the Mre11-Rad50-Nbs1 complex. Science 308: 551-554.
60. Lee M. S, Edwards RA, Thede GL, Glover JN. 2005. Structure of the BRCTrepeat domain of MDC1 and its specificity for the free COOH-terminal end of the g-H2AX histone tail. J Biol Chem 280: 32053-32056.
61. Lee J, Kumagai A, DunphyWG. 2007. The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. J Biol Chem 282: 28036-28044.
62. Lee J. H, Goodarzi AA, Jeggo PA, Paull TT. 2010. 53BP1 promotes ATM activity through direct interactions with the MRN complex. EMBO J 29: 574-585.
63. Lempiainen H., Halazonetis TD. 2009. Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J 28: 3067-3073.
64. Limbo O., Chahwan C, Yamada Y, de Bruin RA, Wittenberg C, Russell P. 2007. Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control doublestrand break repair by homologous recombination. Mol Cell 28: 134-146.
65. Liu Q., Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, Luo G., Carattini-Rivera S, DeMayo F, Bradley A, et al. 2000. Chk1 is an essential kinase that is regulated by Atr and required for the G2/MDNA damage checkpoint. Genes Dev 14: 1448-1459.
66. Liu S., Shiotani B, Lahiri M, Marechal A, Tse A, Leung CC, Glover J. N, Yang XH, Zou L. 2011a. ATR autophosphorylation as a molecular switch for checkpoint activation. Mol Cell 43: 192-202.
67. Liu Y., Vaithiyalingam S, Shi Q, Chazin WJ, Zinkel SS. 2011b. BID binds to replication protein A and stimulates ATR function following replicative stress. Mol Cell Biol 31: 4298-4309.
68. Liu J., Luo S, Zhao H, Liao J, Li J, Yang C, Xu B, Stern DF, Xu X, Ye K. 2012a. Structural mechanism of the phosphorylation-dependent dimerization of the MDC1 forkheadassociated domain. Nucleic Acids Res 40: 3898-3912.
69. Liu S., Song N, Zou L. 2012b. The conserved C terminus of Claspin interacts with Rad9 and promotes rapid activation of Chk1. Cell Cycle 11: 2711-2716.
70. Llorca O., Rivera-Calzada A, Grantham J, Willison KR. 2003. Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an arm-like domain to clamp around double-strandedDNA. Oncogene 22: 3867-3874.
71. Lopes M., Foiani M, Sogo JM. 2006. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol Cell 21: 15-27.
72. Lou Z., Minter-Dykhouse K, Franco S, Gostissa M, Rivera MA, Celeste A, Manis JP, van Deursen J, Nussenzweig A, Paull T. T, et al. 2006. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol Cell 21: 187-200.
73. LovejoyCA, CortezD. 2009. Common mechanisms of PIKK regulation. DNA Repair (Amst) 8: 1004-1008.
74. Lukas J., Lukas C, Bartek J. 2011. More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol 13: 1161-1169.
75. Luo K., Yuan J, Lou Z. 2011. Oligomerization of MDC1 protein is important for proper DNA damage response. J Biol Chem 286: 28192-28199.
76. Mailand N., Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J. 2007. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131: 887-900.
77. Majka J., Niedziela-Majka A, Burgers PM. 2006. The checkpoint clamp activates Mec1 kinase during initiation of the DNA damage checkpoint. Mol Cell 24: 891-901.
78. Matsuoka S., Huang M, Elledge SJ. 1998. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282: 1893-1897.
79. Matsuoka S., Ballif BA, Smogorzewska A, McDonald ER III, Hurov K. E, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y., et al. 2007. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316: 1160-1166.
80. Mattiroli F., Vissers JH, van Dijk WJ, Ikpa P, Citterio E, Vermeulen W., Marteijn JA, Sixma TK. 2012. RNF168 ubiquitinates K13-15 on H2A/H2AX to driveDNAdamage signaling. Cell 150: 1182-1195.
81. McNees CJ, Tejera AM, Martinez P, Murga M, Mulero F, Fernandez-Capetillo O, Blasco MA. 2010. ATR suppresses telomere fragility and recombination but is dispensable for elongation of short telomeres by telomerase. JCell Biol 188: 639-652.
82. Meerang M., Ritz D, Paliwal S, Garajova Z, Bosshard M, Mailand N., Janscak P, Hubscher U, Meyer H, Ramadan K. 2011. The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks. Nat Cell Biol 13: 1376-1382.
83. Meier A., Fiegler H, Munoz P, Ellis P, Rigler D, Langford C, Blasco M. A, Carter N, Jackson SP. 2007. Spreading of mammalian DNA-damage response factors studied by ChIP-chip at damaged telomeres. EMBO J 26: 2707-2718.
84. Melander F., Bekker-Jensen S, Falck J, Bartek J, Mailand N, Lukas J. 2008. Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. J Cell Biol 181: 213-226.
85. Mordes D. A, Cortez D. 2008. Activation of ATR and related PIKKs. Cell Cycle 7: 2809-2812.
86. Mordes D. A, Glick GG, Zhao R, Cortez D. 2008a. TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev 22: 1478-1489.
87. Mordes D. A, Nam EA, Cortez D. 2008b. Dpb11 activates the Mec1-Ddc2 complex. Proc Natl Acad Sci 105: 18730-18734.
88. Morris J. R, Boutell C, Keppler M, Densham R, Weekes D, Alamshah A., Butler L, Galanty Y, Pangon L, Kiuchi T, et al. 2009. The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature 462: 886-890.
89. Munoz M. C, Laulier C, Gunn A, Cheng A, Robbiani DF, Nussenzweig A., Stark JM. 2012. Ring finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1. J Biol Chem 287: 40618-40628.
90. Myers J. S, Cortez D. 2006. Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J Biol Chem 281: 9346-9350.
91. Nam E. A, Cortez D. 2011. ATR signalling: More than meeting at the fork. Biochem J 436: 527-536.
92. Nam E. A, Zhao R, Glick GG, Bansbach CE, Friedman DB, Cortez D. 2011. Thr-1989 phosphorylation is a marker of active ataxia telangiectasia-mutated and Rad3-related (ATR) kinase. J Biol Chem 286: 28707-28714.
93. Namiki Y., Zou L. 2006. ATRIP associates with replication protein A-coated ssDNA through multiple interactions. Proc Natl Acad Sci 103: 580-585.
94. Navadgi-Patil VM, Burgers PM. 2008. Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. J Biol Chem 283: 35853-35859.
95. Navadgi-Patil VM, Burgers PM. 2009. The unstructured Cterminal tail of the 9-1-1 clamp subunit Ddc1 activates Mec1/ATR via two distinct mechanisms. Mol Cell 36: 743-753.
96. Navadgi-Patil VM, Kumar S, Burgers PM. 2011. The unstructured C-terminal tail of yeast Dpb11 (human TopBP1) protein is dispensable for DNA replication and the S phase checkpoint but required for the G2/M checkpoint. J Biol Chem 286: 40999-41007.
97. Paulsen R. D, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, Hesley JA, Miller SC, Cromwell EF, Solow-Cordero DE, et al. 2009. A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell 35: 228-239.
98. Pellegrini M., Celeste A, Difilippantonio S, Guo R, WangW, Feigenbaum L., Nussenzweig A. 2006. Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo. Nature 443: 222-225.
99. Peng G., Dai H, Zhang W, Hsieh HJ, Pan MR, Park YY, Tsai RY, Bedrosian I, Lee JS, Ira G, et al. 2012. Human nuclease/ helicase DNA2 alleviates replication stress by promoting DNA end resection. Cancer Res 72: 2802-2813.
100. Perry J., Kleckner N. 2003. The ATRs, ATMs, and TORs are giant HEATrepeat proteins. Cell 112: 151-155.
101. Pires I. M, Olcina MM, Anbalagan S, Pollard JR, Reaper PM, Charlton P. A, McKenna WG, Hammond EM. 2012. Targeting radiation-resistant hypoxic tumour cells through ATR inhibition. Br J Cancer 107: 291-299.
102. Puddu F., Granata M, Di Nola L, Balestrini A, Piergiovanni G, Lazzaro F, Giannattasio M, Plevani P, Muzi-Falconi M. 2008. Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint. Mol Cell Biol 28: 4782-4793.
103. Reaper P. M, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. 2011. Selective killing of ATM-or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol 7: 428-430.
104. Reinhardt H. C, Aslanian AS, Lees JA, Yaffe MB. 2007. p53-deficient cells rely on ATM-and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell 11: 175-189.
105. Rivera-Calzada A, Maman JD, Spagnolo L, Pearl LH, Llorca O. 2005. Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Structure 13: 243-255.
106. Sartori A. A, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP. 2007. Human CtIP promotesDNA end resection. Nature 450: 509-514.
107. Savic V., Yin B, Maas NL, Bredemeyer AL, Carpenter AC, Helmink B. A, Yang-Lott KS, Sleckman BP, Bassing CH. 2009. Formation of dynamic g-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin. Mol Cell 34: 298-310.
108. Schiller C. B, Lammens K, Guerini I, Coordes B, Feldmann H, Schlauderer F, Mockel C, Schele A, Strasser K, Jackson SP, et al. 2012. Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling. Nat Struct Mol Biol 19: 693-700.
109. Shigechi T., Tomida J, Sato K, Kobayashi M, Eykelenboom JK, Pessina F, Zhang Y, Uchida E, Ishiai M, Lowndes NF, et al. 2012. ATR-ATRIP kinase complex triggers activation of the Fanconi anemia DNA repair pathway. Cancer Res 72: 1149-1156.
110. Shiloh Y. 2003. ATM and related protein kinases: Safeguarding genome integrity. Nat Rev Cancer 3: 155-168.
111. Shin M. H, Yuan M, Zhang H, Margolick JB, Kai M. 2012. ATM-dependent phosphorylation of the checkpoint clamp regulates repair pathways and maintains genomic stability. Cell Cycle 11: 1796-1803.
112. Shiotani B., Zou L. 2009. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol Cell 33: 547-558.
113. Sibanda B. L, Chirgadze DY, Blundell TL. 2009. Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEATrepeats. Nature 463: 118-121.
114. Slabicki M., Theis M, Krastev DB, Samsonov S, Mundwiller E, Junqueira M, Paszkowski-Rogacz M, Teyra J, Heninger AK, Poser I, et al. 2010. A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. PLoS Biol 8: e1000408.
115. Smith J., Tho LM, Xu N, GillespieDA. 2010. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res 108: 73-112.
116. Smolka M. B, Albuquerque CP, Chen SH, Zhou H. 2007. Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proc Natl Acad Sci 104: 10364-10369.
117. So S., Davis AJ, Chen DJ. 2009. Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites. J Cell Biol 187: 977-990.
118. Sobhian B., Shao G, Lilli DR, Culhane AC, Moreau LA, Xia B, Livingston DM, Greenberg RA. 2007. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316: 1198-1202.
119. Sorensen C. S, Hansen LT, Dziegielewski J, SyljuasenRG, Lundin C, Bartek J, Helleday T. 2005. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 7: 195-201.
120. Spycher C., Miller ES, Townsend K, Pavic L, Morrice NA, Janscak P., Stewart GS, Stucki M. 2008. Constitutive phosphorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin. J Cell Biol 181: 227-240.
121. Stewart G.S. 2009. Solving the RIDDLE of 53BP1 recruitment to sites of damage. Cell Cycle 8: 1532-1538.
122. Stewart G. S, Wang B, Bignell CR, Taylor AM, Elledge SJ. 2003. MDC1 is a mediator of the mammalianDNA damage checkpoint. Nature 421: 961-966.
123. Stiff T, Walker SA, Cerosaletti K, Goodarzi AA, Petermann E, Concannon P., O'Driscoll M, Jeggo PA. 2006. ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J 25: 5775-5782.
124. Stokes M. P, Rush J, Macneill J, Ren JM, Sprott K, Nardone J, Yang V., Beausoleil SA, Gygi SP, Livingstone M, et al. 2007. Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci 104: 19855-19860.
125. Stracker T. H, Morales M, Couto SS, Hussein H, Petrini JH. 2007. The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex. Nature 447: 218-221.
126. Stucki M., Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP. 2005. MDC1directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123: 1213-1226.
127. Sun Y., Jiang X, Chen S, Fernandes N, Price BD. 2005. A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci 102: 13182-13187.
128. Sun Y., Xu Y, Roy K, Price BD. 2007. DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity. Mol Cell Biol 27, 8502-8509.
129. Sun Y., Jiang X, Xu Y, Ayrapetov MK, Moreau LA, Whetstine JR, Price BD. 2009. Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat Cell Biol 11: 1376-1382.
130. Symington L. S, Gautier J. 2011. Double-strand break end resection and repair pathway choice. Annu Rev Genet 45: 247-271.
131. Takai H, Wang RC, Takai KK, Yang H, de Lange T. 2007. Tel2 regulates the stability of PI3K-related protein kinases. Cell 131: 1248-1259.
132. Takai H., Xie Y, de Lange T, Pavletich NP. 2010. Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes. Genes Dev 24: 2019-2030.
133. Tomimatsu N, Mukherjee B, Burma S. 2009. Distinct roles of ATR and DNA-PKcs in triggering DNA damage responses in ATM-deficient cells. EMBO Rep 10: 629-635.
134. Tomimatsu N., Mukherjee B, Deland K, Kurimasa A, Bolderson E, Khanna KK, Burma S. 2012. Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions. DNA Repair (Amst) 11: 441-448.
135. Uziel T., Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y. 2003. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 22: 5612-5621.
136. Wang B., Elledge SJ. 2007. Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/ Brcc36 complex in response to DNA damage. Proc Natl Acad Sci 104: 20759-20763.
137. Wang B., Matsuoka S, Carpenter PB, Elledge SJ. 2002. 53BP1, a mediator of the DNA damage checkpoint. Science 298: 1435-1438.
138. Wang H., Powell SN, Iliakis G, Wang Y. 2004. ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining. Cancer Res 64: 7139-7143.
139. Wang B., Matsuoka S, Ballif BA, Zhang D, Smogorzewska A, Gygi S. P, Elledge SJ. 2007. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 316: 1194-1198.
140. Wang J., Gong Z, Chen J. 2011. MDC1 collaborates with TopBP1 in DNA replication checkpoint control. J Cell Biol 193: 267-273.
141. Ward I. M, Chen J. 2001. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 276: 47759-47762.
142. Wawrousek K. E, Fortini BK, Polaczek P, Chen L, Liu Q, Dunphy W. G, Campbell JL. 2010. Xenopus DNA2 is a helicase/nuclease that is found in complexes with replication proteins And-1/Ctf4 and Mcm10 and DSB response proteins Nbs1 and ATM. Cell Cycle 9: 1156-1166.
143. Williams D. R, Lee KJ, Shi, J, Chen DJ, Stewart PL. 2008. Cryo-EM structure of the DNA-dependent protein kinase catalytic subunit at subnanometer resolution reveals a helices and insight into DNA binding. Structure 16: 468-477.
144. Wu L., Luo K, Lou Z, Chen J. 2008. MDC1 regulates intra-Sphase checkpoint by targeting NBS1 to DNA doublestrand breaks. Proc Natl Acad Sci 105: 11200-11205.
145. Yoo H. Y, Kumagai A, Shevchenko A, Dunphy WG. 2007. Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM. J Biol Chem 282: 17501-17506.
146. Yoo H. Y, Kumagai A, Shevchenko A, Dunphy WG. 2009. The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM. Mol Biol Cell 20: 2351-2360.
147. You Z., Chahwan C, Bailis J, Hunter T, Russell P. 2005. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol 25: 5363-5379.
148. You Z., Bailis JM, Johnson SA, Dilworth SM, Hunter T. 2007. Rapid activation of ATMonDNA flanking double-strand breaks. Nat Cell Biol 9: 1311-1318.
149. You Z., Shi LZ, Zhu Q, Wu P, ZhangYW, Basilio A, Tonnu N, Verma I. M, Berns MW, Hunter T. 2009. CtIP links DNA double-strand break sensing to resection. Mol Cell 36: 954-969.
150. Zha S., Guo C, Boboila C, Oksenych V, Cheng HL, Zhang Y, Wesemann D. R, Yuen G, Patel H, Goff PH, et al. 2011. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature 469: 250-254.
151. Zhang N., Kaur R, Akhter S, Legerski RJ. 2009. Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. EMBO Rep 10: 1029-1035.
152. Zhou B. B, Elledge SJ. 2000. The DNA damage response: Putting checkpoints in perspective. Nature 408: 433-439.
153. Zou L., Elledge SJ. 2003. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300: 1542-1548.
154. Zou L., Liu D, Elledge SJ. 2003. Replication protein A-mediated recruitment and activation of Rad17 complexes. Proc Natl Acad Sci 100: 13827-13832.