The ATM regulated DNA damage response pathway as a chemo- and radiosensitisation target

Bibliography

• Zhou BB, Bartek J. Targeting the checkpoint kinases: chemosensitization versus chemoprotection. Nat Rev Cancer 2004;4(3):216-25
   PubMed Web of Science ®Google Scholar
• Blasina A, Price BD, Turenne GA, McGowan CH. Caffeine inhibits the checkpoint kinase ATM. Curr Biol 1999;9(19):1135-8
   PubMed Web of Science ®Google Scholar
• Gaudin D, Yielding KL. Response of a “resistant” plasmacytoma to alkylating agents and x-ray in combination with the “excision” repair inhibitors caffeine and chloroquine. Proc Soc Exp Biol Med 1969;131(4):1413-16
   PubMed Web of Science ®Google Scholar
• Sarkaria JN, Tibbetts RS, Busby EC, et al. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res 1998;58(19):4375-82
   PubMed Web of Science ®Google Scholar
• Zhou BB, Chaturvedi P, Spring K, et al. Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity. J Biol Chem 2000;275(14):10342-8
   PubMed Web of Science ®Google Scholar
• Kawabe T. G2 checkpoint abrogators as anticancer drugs. Mol Cancer Ther 2004;3(4):513-19
   PubMed Web of Science ®Google Scholar
• Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 2008;9(10):759-69
   PubMed Web of Science ®Google Scholar
• Savitsky K, Bar-Shira A, Gilad S, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995;268(5218):1749-53
   PubMed Web of Science ®Google Scholar
• Lee JH, Paull TT. Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene 2007;26(56):7741-8
   PubMed Web of Science ®Google Scholar
• Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 2003;421(6922):499-506
   PubMed Web of Science ®Google Scholar
• Kozlov SV, Graham ME, Peng C, et al. Involvement of novel autophosphorylation sites in ATM activation. EMBO J 2006;25(15):3504-14
   PubMed Web of Science ®Google Scholar
• Sun Y, Jiang X, Chen S, et al. A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci USA 2005;102(37):13182-7
   PubMed Web of Science ®Google Scholar
• Lavin MF, Birrell G, Chen P, et al. ATM signaling and genomic stability in response to DNA damage. Mutat Res 2005;569(1-2):123-32
   PubMed Web of Science ®Google Scholar
• Lavin MF, Shiloh Y. The genetic defect in ataxia-telangiectasia. Annu Rev Immunol 1997;15:177-202
   PubMed Web of Science ®Google Scholar
• Zhang N, Chen P, Khanna KK, et al. Isolation of full-length ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype. Proc Natl Acad Sci USA 1997;94(15):8021-6
   PubMed Web of Science ®Google Scholar
• Ziv Y, Bar-Shira A, Pecker I, et al. Recombinant ATM protein complements the cellular A-T phenotype. Oncogene 1997;15(2):159-67
   PubMed Web of Science ®Google Scholar
• Banin S, Moyal L, Shieh S, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 1998;281(5383):1674-7
   PubMed Web of Science ®Google Scholar
• Canman CE, Lim DS, Cimprich KA, et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 1998;281(5383):1677-9
   PubMed Web of Science ®Google Scholar
• Kurz EU, Lees-Miller SP. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair 2004;3(8-9):889-900
   PubMed Web of Science ®Google Scholar
• Bonilla CY, Melo JA, Toczyski DP. Colocalization of sensors is sufficient to activate the DNA damage checkpoint in the absence of damage. Mol Cell 2008;30(3):267-76
   PubMed Web of Science ®Google Scholar
• Soutoglou E, Misteli T. Activation of the cellular DNA damage response in the absence of DNA lesions. Science 2008;320(5882):1507-10
   PubMed Web of Science ®Google Scholar
• Kanu N, Behrens A. ATMINistrating ATM signalling: regulation of ATM by ATMIN. Cell Cycle 2008;7(22):3483-6
   PubMed Web of Science ®Google Scholar
• Berkovich E, Monnat RJ Jr, Kastan MB. Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol 2007;9(6):683-90
   PubMed Web of Science ®Google Scholar
• Cann KL, Hicks GG. Regulation of the cellular DNA double-strand break response. Biochem Cell Biol 2007;85(6):663-74
   PubMed Web of Science ®Google Scholar
• Burma S, Chen BP, Murphy M, et al. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001;276(45):42462-7
   PubMed Web of Science ®Google Scholar
• Anderson L, Henderson C, Adachi Y. Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage. Mol Cell Biol 2001;21(5):1719-29
   PubMed Web of Science ®Google Scholar
• Schultz LB, Chehab NH, Malikzay A, Halazonetis TD. p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J Cell Biol 2000;151(7):1381-90
   PubMed Web of Science ®Google Scholar
• Bassing CH, Suh H, Ferguson DO, et al. Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 2003;114(3):359-70
   PubMed Web of Science ®Google Scholar
• Celeste A, Fernandez-Capetillo O, Kruhlak MJ, et al. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol 2003;5(7):675-9
   PubMed Web of Science ®Google Scholar
• Lou Z, Minter-Dykhouse K, Franco S, et al. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol Cell 2006;21(2):187-200
   PubMed Web of Science ®Google Scholar
• Lukas C, Melander F, Stucki M, et al. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J 2004;23(13):2674-83
   PubMed Web of Science ®Google Scholar
• Stucki M, Jackson SP. gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes. DNA Repair 2006;5(5):534-43
   PubMed Web of Science ®Google Scholar
• Huen MS, Grant R, Manke I, et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 2007;131(5):901-14
   PubMed Web of Science ®Google Scholar
• Kolas NK, Chapman JR, Nakada S, et al. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 2007;318(5856):1637-40
   PubMed Web of Science ®Google Scholar
• Mailand N, Bekker-Jensen S, Faustrup H, et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 2007;131(5):887-900
   PubMed Web of Science ®Google Scholar
• Goldberg M, Stucki M, Falck J, et al. MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 2003;421(6926):952-6
   PubMed Web of Science ®Google Scholar
• Xu B, O'Donnell AH, Kim ST, Kastan MB. Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer Res 2002;62(16):4588-91
   PubMed Web of Science ®Google Scholar
• Mirzoeva OK, Petrini JH. DNA damage-dependent nuclear dynamics of the Mre11 complex. Mol Cell Biol 2001;21(1):281-8
   PubMed Web of Science ®Google Scholar
• Cerosaletti K, Wright J, Concannon P. Active role for nibrin in the kinetics of atm activation. Mol Cell Biol 2006;26(5):1691-9
   PubMed Web of Science ®Google Scholar
• Lee JH, Paull TT. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 2004;304(5667):93-6
   PubMed Web of Science ®Google Scholar
• Lee JH, Paull TT. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 2005;308(5721):551-4
   PubMed Web of Science ®Google Scholar
• Uziel T, Lerenthal Y, Moyal L, et al. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 2003;22(20):5612-21
   PubMed Web of Science ®Google Scholar
• Lim DS, Kim ST, Xu B, et al. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature 2000;404(6778):613-7
   PubMed Web of Science ®Google Scholar
• Yazdi PT, Wang Y, Zhao S, et al. SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev 2002;16(5):571-82
   PubMed Web of Science ®Google Scholar
• Li L, Zou L. Sensing, signaling, and responding to DNA damage: organization of the checkpoint pathways in mammalian cells. J Cell Biochem 2005;94(2):298-306
   PubMed Web of Science ®Google Scholar
• Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997;88(3):323-31
   PubMed Web of Science ®Google Scholar
• Siliciano JD, Canman CE, Taya Y, et al. DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev 1997;11(24):3471-81
   PubMed Web of Science ®Google Scholar
• Chehab NH, Malikzay A, Appel M, Halazonetis TD. Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev 2000;14(3):278-88
   PubMed Web of Science ®Google Scholar
• Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD. Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci USA 1999;96(24):13777-82
   PubMed Web of Science ®Google Scholar
• Matsuoka S, Huang M, Elledge SJ. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 1998;282(5395):1893-7
   PubMed Web of Science ®Google Scholar
• Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature 1997;387(6630):296-9
   PubMed Web of Science ®Google Scholar
• Khosravi R, Maya R, Gottlieb T, et al. Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc Natl Acad Sci USA 1999;96(26):14973-7
   PubMed Web of Science ®Google Scholar
• el-Deiry WS, Tokino T, Velculescu VE, et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993;75(4):817-25
   PubMed Web of Science ®Google Scholar
• Bartek J, Lukas J. Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr Opin Cell Biol 2001;13(6):738-47
   PubMed Web of Science ®Google Scholar
• Bartek J, Lukas J. Pathways governing G1/S transition and their response to DNA damage. FEBS Lett 2001;490(3):117-22
   PubMed Web of Science ®Google Scholar
• Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 1995;9(10):1149-63
   PubMed Web of Science ®Google Scholar
• Chang BD, Swift ME, Shen M, et al. Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci USA 2002;99(1):389-94
   PubMed Web of Science ®Google Scholar
• Falck J, Mailand N, Syljuasen RG, et al. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 2001;410(6830):842-7
   PubMed Web of Science ®Google Scholar
• Mailand N, Falck J, Lukas C, et al. Rapid destruction of human Cdc25A in response to DNA damage. Science 2000;288(5470):1425-9
   PubMed Web of Science ®Google Scholar
• Meulmeester E, Pereg Y, Shiloh Y, Jochemsen AG. ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell Cycle 2005;4(9):1166-70
   PubMed Web of Science ®Google Scholar
• Okamoto K, Kashima K, Pereg Y, et al. DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation. Mol Cell Biol 2005;25(21):9608-20
   PubMed Web of Science ®Google Scholar
• Stad R, Ramos YF, Little N, et al. Hdmx stabilizes Mdm2 and p53. J Biol Chem 2000;275(36):28039-44
   PubMed Web of Science ®Google Scholar
• Danovi D, Meulmeester E, Pasini D, et al. Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity. Mol Cell Biol 2004;24(13):5835-43
   PubMed Web of Science ®Google Scholar
• Ramos YF, Stad R, Attema J, et al. Aberrant expression of HDMX proteins in tumor cells correlates with wild-type p53. Cancer Res 2001;61(5):1839-42
   PubMed Web of Science ®Google Scholar
• Shvarts A, Steegenga WT, Riteco N, et al. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J 1996;15(19):5349-57
   PubMed Web of Science ®Google Scholar
• de Graaf P, Little NA, Ramos YF, et al. Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2. J Biol Chem 2003;278(40):38315-24
   PubMed Web of Science ®Google Scholar
• Kawai H, Wiederschain D, Kitao H, et al. DNA damage-induced MDMX degradation is mediated by MDM2. J Biol Chem 2003;278(46):45946-53
   PubMed Web of Science ®Google Scholar
• Pan Y, Chen J. MDM2 promotes ubiquitination and degradation of MDMX. Mol Cell Biol 2003;23(15):5113-21
   PubMed Web of Science ®Google Scholar
• Pereg Y, Shkedy D, de Graaf P, et al. Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage. Proc Natl Acad Sci USA 2005;102(14):5056-61
   PubMed Web of Science ®Google Scholar
• Meulmeester E, Maurice MM, Boutell C, et al. Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2. Mol Cell 2005;18(5):565-76
   PubMed Web of Science ®Google Scholar
• Cimprich KA, Cortez D. ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 2008;9(8):616-27
   PubMed Web of Science ®Google Scholar
• Hurley PJ, Bunz F. ATM and ATR: components of an integrated circuit. Cell Cycle 2007;6(4):414-17
   PubMed Web of Science ®Google Scholar
• Hurley PJ, Wilsker D, Bunz F. Human cancer cells require ATR for cell cycle progression following exposure to ionizing radiation. Oncogene 2007;26(18):2535-42
   PubMed Web of Science ®Google Scholar
• Brown EJ, Baltimore D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev 2000;14(4):397-402
   PubMed Web of Science ®Google Scholar
• de Klein A, Muijtjens M, van Os R, et al. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr Biol 2000;10(8):479-82
   PubMed Web of Science ®Google Scholar
• Cuadrado M, Martinez-Pastor B, Fernandez-Capetillo O. “ATR activation in response to ionizing radiation: still ATM territory”. Cell Div 2006;1(1):7
   PubMedGoogle Scholar
• Liu Q, Guntuku S, Cui XS, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev 2000;14(12):1448-59
   PubMedGoogle Scholar
• Lopez-Girona A, Tanaka K, Chen XB, et al. Serine-345 is required for Rad3-dependent phosphorylation and function of checkpoint kinase Chk1 in fission yeast. Proc Natl Acad Sci USA 2001;98(20):11289-94
   PubMed Web of Science ®Google Scholar
• Zhao H, Watkins JL, Piwnica-Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci USA 2002;99(23):14795-800
   PubMed Web of Science ®Google Scholar
• Uto K, Inoue D, Shimuta K, et al. Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism. EMBO J 2004;23(16):3386-96
   PubMed Web of Science ®Google Scholar
• Agami R, Bernards R. Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage. Cell 2000;102(1):55-66
   PubMed Web of Science ®Google Scholar
• Pontano LL, Aggarwal P, Barbash O, et al. Genotoxic stress-induced cyclin D1 phosphorylation and proteolysis are required for genomic stability. Mol Cell Biol 2008;28(23):7245-58
   PubMed Web of Science ®Google Scholar
• Alao JP. The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer 2007;6:24
   PubMed Web of Science ®Google Scholar
• Painter RB, Young BR. Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc Natl Acad Sci USA 1980;77(12):7315-17
   PubMed Web of Science ®Google Scholar
• Carney JP, Maser RS, Olivares H, et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 1998;93(3):477-86
   PubMed Web of Science ®Google Scholar
• Stewart GS, Maser RS, Stankovic T, et al. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 1999;99(6):577-87
   PubMed Web of Science ®Google Scholar
• Varon R, Vissinga C, Platzer M, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 1998;93(3):467-76
   PubMed Web of Science ®Google Scholar
• Jackson JR, Gilmartin A, Imburgia C, et al. An indolocarbazole inhibitor of human checkpoint kinase (Chk1) abrogates cell cycle arrest caused by DNA damage. Cancer Res 2000;60(3):566-72
   PubMed Web of Science ®Google Scholar
• Pandita TK, Lieberman HB, Lim DS, et al. Ionizing radiation activates the ATM kinase throughout the cell cycle. Oncogene 2000;19(11):1386-91
   PubMed Web of Science ®Google Scholar
• Wu X, Ranganathan V, Weisman DS, et al. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature 2000;405(6785):477-82
   PubMed Web of Science ®Google Scholar
• Zhao S, Weng YC, Yuan SS, et al. Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products. Nature 2000;405(6785):473-7
   PubMed Web of Science ®Google Scholar
• Lehmann AR. The role of SMC proteins in the responses to DNA damage. DNA Repair 2005;4(3):309-14
   PubMed Web of Science ®Google Scholar
• Kim ST, Xu B, Kastan MB. Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev 2002;16(5):560-70
   PubMed Web of Science ®Google Scholar
• Nakanishi K, Taniguchi T, Ranganathan V, et al. Interaction of FANCD2 and NBS1 in the DNA damage response. Nat Cell Biol 2002;4(12):913-20
   PubMed Web of Science ®Google Scholar
• Bartek J, Lukas C, Lukas J. Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 2004;5(10):792-804
   PubMed Web of Science ®Google Scholar
• Donzelli M, Draetta GF. Regulating mammalian checkpoints through Cdc25 inactivation. EMBO Rep 2003;4(7):671-7
   PubMed Web of Science ®Google Scholar
• Sorensen CS, Syljuasen RG, Lukas J, Bartek J. ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage. Cell Cycle 2004;3(7):941-5
   PubMed Web of Science ®Google Scholar
• Sorensen CS, Syljuasen RG, Falck J, et al. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell 2003;3(3):247-58
   PubMed Web of Science ®Google Scholar
• Busino L, Donzelli M, Chiesa M, et al. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 2003;426(6962):87-91
   PubMed Web of Science ®Google Scholar
• Jin J, Shirogane T, Xu L, et al. SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev 2003;17(24):3062-74
   PubMed Web of Science ®Google Scholar
• Dalal SN, Schweitzer CM, Gan J, DeCaprio JA. Cytoplasmic localization of human cdc25C during interphase requires an intact 14-3-3 binding site. Mol Cell Biol 1999;19(6):4465-79
   PubMed Web of Science ®Google Scholar
• Peng CY, Graves PR, Thoma RS, et al. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 1997;277(5331):1501-5
   PubMed Web of Science ®Google Scholar
• Chan TA, Hermeking H, Lengauer C, et al. 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature 1999;401(6753):616-20
   PubMed Web of Science ®Google Scholar
• Reinhardt HC, Aslanian AS, Lees JA, Yaffe MB. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell 2007;11(2):175-89
   PubMed Web of Science ®Google Scholar
• Jackson JR, Zhou BB. G2 checkpoint control: checking in to the last resort for DNA damage. Cancer Biol Ther 2004;3(3):314-16
   PubMed Web of Science ®Google Scholar
• Alao JP, Sunnerhagen P. Rad3 and Sty1 function in Schizosaccharomyces pombe: an integrated response to DNA damage and environmental stress? Mol Microbiol 2008;68(2):246-54
   PubMed Web of Science ®Google Scholar
• Manke IA, Nguyen A, Lim D, et al. MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation. Mol Cell 2005;17(1):37-48
   PubMed Web of Science ®Google Scholar
• Sidi S, Sanda T, Kennedy RD, et al. Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3. Cell 2008;133(5):864-77
   PubMed Web of Science ®Google Scholar
• Kuhne M, Riballo E, Rief N, et al. A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res 2004;64(2):500-8
   PubMed Web of Science ®Google Scholar
• Lieber MR. The mechanism of human nonhomologous DNA end joining. J Biol Chem 2008;283(1):1-5
   PubMed Web of Science ®Google Scholar
• Riballo E, Kuhne M, Rief N, et al. A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. Mol Cell 2004;16(5):715-24
   PubMed Web of Science ®Google Scholar
• Moshous D, Callebaut I, de Chasseval R, et al. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell 2001;105(2):177-86
   PubMed Web of Science ®Google Scholar
• Jeggo PA, Lobrich M. Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability. DNA Repair 2006;5(9-10):1192-8
   PubMed Web of Science ®Google Scholar
• San Filippo J, Sung P, Klein H. Mechanism of eukaryotic homologous recombination. Annu Rev Biochem 2008;77:229-57
   PubMed Web of Science ®Google Scholar
• Sorensen CS, Hansen LT, Dziegielewski J, et al. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 2005;7(2):195-201
   PubMed Web of Science ®Google Scholar
• Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature 2000;408(6811):433-9
   PubMed Web of Science ®Google Scholar
• Schuler M, Green DR. Transcription, apoptosis and p53: catch-22. Trends Genet 2005;21(3):182-7
   PubMed Web of Science ®Google Scholar
• Bree RT, Neary C, Samali A, Lowndes NF. The switch from survival responses to apoptosis after chromosomal breaks. DNA Repair 2004;3(8-9):989-95
   PubMed Web of Science ®Google Scholar
• Chen C, Shimizu S, Tsujimoto Y, Motoyama N. Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage. Biochem Biophys Res Commun 2005;333(2):427-31
   PubMed Web of Science ®Google Scholar
• Hirao A, Kong YY, Matsuoka S, et al. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 2000;287(5459):1824-7
   PubMed Web of Science ®Google Scholar
• Takai H, Naka K, Okada Y, et al. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J 2002;21(19):5195-205
   PubMed Web of Science ®Google Scholar
• Keramaris E, Hirao A, Slack RS, et al. Ataxia telangiectasia-mutated protein can regulate p53 and neuronal death independent of Chk2 in response to DNA damage. J Biol Chem 2003;278(39):37782-9
   PubMed Web of Science ®Google Scholar
• Antoni L, Sodha N, Collins I, Garrett MD. CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin? Nat Rev Cancer 2007;7(12):925-36
   PubMed Web of Science ®Google Scholar
• Cresenzi E, Palumbo G, de Boer J, Brady HJ. Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy. Clin Cancer Res 2008;14(6):1877-87
   PubMed Web of Science ®Google Scholar
• Aliouat-Denis CM, Dendouga N, Van den Wyngaert I, et al. p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2. Mol Cancer Res 2005;3(11):627-34
   PubMed Web of Science ®Google Scholar
• d'Adda di Fagagna F, Reaper Pm, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003;426(6963):194-8
   PubMed Web of Science ®Google Scholar
• Sarkaria JN, Eshleman JS. ATM as a target for novel radiosensitizers. Semin Radiat Oncol 2001;11(4):316-27
   PubMed Web of Science ®Google Scholar
• Taylor AM, Harnden DG, Arlett CF, et al. Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity. Nature 1975;258(5534):427-9
   PubMed Web of Science ®Google Scholar
• Cortez D. Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases. J Biol Chem 2003;278(39):37139-45
   PubMed Web of Science ®Google Scholar
• Hickson I, Zhao Y, Richardson CJ, et al. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 2004;64(24):9152-9
   PubMed Web of Science ®Google Scholar
• Hitomi M, Yang K, Stacey AW, Stacey DW. Phosphorylation of cyclin D1 regulated by ATM or ATR controls cell cycle progression. Mol Cell Biol 2008;28(17):5478-93
   PubMed Web of Science ®Google Scholar
• Matsuoka S, Ballif BA, Smogorzewska A, et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007;316(5828):1160-6
   PubMed Web of Science ®Google Scholar
• Busby EC, Leistritz DF, Abraham RT, et al. The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1. Cancer Res 2000;60(8):2108-12
   PubMed Web of Science ®Google Scholar
• Graves PR, Yu L, Schwarz JK, et al. The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. J Biol Chem 2000;275(8):5600-5
   PubMed Web of Science ®Google Scholar
• Tsuchida E, Tsuchida M, Urano M. Synergistic cytotoxicity between a protein kinase C inhibitor, UCN-01, and monoclonal antibody to the epidermal growth factor receptor on MDA-468 cells. Cancer Biother Radiopharm 1997;12(2):117-21
   PubMed Web of Science ®Google Scholar
• Wang Q, Fan S, Eastman A, et al. UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst 1996;88(14):956-65
   PubMed Web of Science ®Google Scholar
• Senderowicz AM. Small-molecule cyclin-dependent kinase modulators. Oncogene 2003;22(42):6609-20
   PubMed Web of Science ®Google Scholar
• Welch S, Hirte HW, Carey MS, et al. UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: a study of the Princess Margaret Hospital Phase II consortium. Gynecol Oncol 2007;106(2):305-10
   PubMed Web of Science ®Google Scholar
• Edelman MJ, Bauer KS Jr, Wu S, et al. Phase I and pharmacokinetic study of 7-hydroxystaurosporine and carboplatin in advanced solid tumors. Clin Cancer Res 2007;13(9):2667-74
   PubMed Web of Science ®Google Scholar
• Perez RP, Lewis LD, Beelen AP, et al. Modulation of cell cycle progression in human tumors: a pharmacokinetic and tumor molecular pharmacodynamic study of cisplatin plus the Chk1 inhibitor UCN-01 (NSC 638850). Clin Cancer Res 2006;12(23):7079-85
   PubMed Web of Science ®Google Scholar
• Chen Z, Xiao Z, Gu WZ, et al. Selective Chk1 inhibitors differentially sensitize p53-deficient cancer cells to cancer therapeutics. Int J Cancer 2006;119(12):2784-94
   PubMed Web of Science ®Google Scholar
• Kohn EA, Yoo CJ, Eastman A. The protein kinase C inhibitor Go6976 is a potent inhibitor of DNA damage-induced S and G2 cell cycle checkpoints. Cancer Res 2003;63(1):31-5
   PubMed Web of Science ®Google Scholar
• Chen JS, Lin SY, Tso WL, et al. Checkpoint kinase 1-mediated phosphorylation of Cdc25C and bad proteins are involved in antitumor effects of loratadine-induced G2/M phase cell-cycle arrest and apoptosis. Mol Carcinog 2006;45(7):461-78
   PubMed Web of Science ®Google Scholar
• Matthews DJ, Yakes FM, Chen J, et al. Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo. Cell Cycle 2007;6(1):104-10
   PubMed Web of Science ®Google Scholar
• Carlessi L, Buscemi G, Larson G, et al. Biochemical and cellular characterization of VRX0466617, a novel and selective inhibitor for the checkpoint kinase Chk2. Mol Cancer Ther 2007;6(3):935-44
   PubMed Web of Science ®Google Scholar
• Arienti KL, Brunmark A, Axe FU, et al. Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles. J Med Chem 2005;48(6):1873-85
   PubMed Web of Science ®Google Scholar
• D'Amours D, Jackson SP. The Mre11 complex: at the crossroads of dna repair and checkpoint signalling. Nat Rev Mol Cell Biol 2002;3(5):317-27
   PubMed Web of Science ®Google Scholar
• Xiao Z, Xue J, Sowin TJ, Zhang H. Differential roles of checkpoint kinase 1, checkpoint kinase 2, and mitogen-activated protein kinase-activated protein kinase 2 in mediating DNA damage-induced cell cycle arrest: implications for cancer therapy. Mol Cancer Ther 2006;5(8):1935-43
   PubMed Web of Science ®Google Scholar
• Bartek J, Lukas J, Bartkova J. DNA damage response as an anti-cancer barrier: damage threshold and the concept of ‘conditional haploinsufficiency’. Cell Cycle 2007;6(19):2344-7
   PubMed Web of Science ®Google Scholar
• Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science 2008;319(5868):1352-5
   PubMed Web of Science ®Google Scholar
• Helleday T, Petermann E, Lundin C, et al. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 2008;8(3):193-204
   PubMed Web of Science ®Google Scholar
• Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007;26(37):5541-52
   PubMed Web of Science ®Google Scholar
• Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov 2003;2(9):717-26
   PubMed Web of Science ®Google Scholar