Targeting abnormal DNA double strand break repair in cancer

Cellular and Molecular Life Sciences

Volumn 67, Issue 21, 2010, Pages 3699-3710

  Rassool, Feyruz V ^a   Tomkinson, Alan E ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Homologous recombination; Non homologous end joining

Indexed keywords

2 (2 METHYL 2 PYRROLIDINYL) 1H BENZIMIDAZOLE 4 CARBOXAMIDE; 2 MORPHOLINO 6 (1 THIANTHRENYL) 4 PYRANONE; 8 FLUORO 3,4 DIHYDRO 2 [4 (METHYLAMINOMETHYL)PHENYL]PYRROLO[3,4,5 E,F][2]BENZAZEPIN 6(5H) ONE; ATM PROTEIN; BRCA1 PROTEIN; BRCA2 PROTEIN; CAMPTOTHECIN; ETOPOSIDE; IC 87361; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NU 7441; OLAPARIB; PROTEIN KINASE INHIBITOR; PROTEIN P53; RAD51 PROTEIN; RAD54 PROTEIN; UNCLASSIFIED DRUG; XRCC3 PROTEIN;

BLOOM SYNDROME; BREAST CANCER; CANCER GROWTH; CANCER SUSCEPTIBILITY; CANCER THERAPY; CHEMOSENSITIVITY; CHROMOSOME ABERRATION; CLINICAL TRIAL; DNA CROSS LINKING; DNA REPAIR; DNA REPLICATION; DOUBLE STRANDED DNA BREAK; DRUG DOSE COMPARISON; FANCONI ANEMIA; GENOMIC INSTABILITY; HOMOLOGOUS RECOMBINATION; HOMOLOGY DIRECTED REPAIR; HUMAN; IONIZING RADIATION; NONHOMOLOGOUS END JOINING; NONHUMAN; OVARY CANCER; PROGRESSION FREE SURVIVAL; REVIEW; SOLID TUMOR; TUMOR; TUMOR REGRESSION;

ANIMALS; ANTINEOPLASTIC AGENTS; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; HUMANS; NEOPLASMS;

EID: 78149468116     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-010-0493-5     Document Type: Review

References (129)

1. KK Khanna SP Jackson 2001 DNA double-strand breaks: signaling, repair and the cancer connection Nat Genet 27 247 254 11242102
2. M O'Driscoll PA Jeggo 2006 The role of double-strand break repair-insights from human genetics Nat Rev Genet 7 45 54 16369571
3. PA Futreal Q Liu D Shattuck-Eidens C Cochran K Harshman S Tavtigian LM Bennett A Haugen-Strano J Swensen Y Miki, et al. 1994 BRCA1 mutations in primary breast and ovarian carcinomas Science 266 120 122 7939630
4. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability-an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11:220-228
5. AJ Hartlerode R Scully 2009 Mechanisms of double-strand break repair in somatic mammalian cells Biochem J 423 157 168 19772495
6. KL Keller TL Overbeck-Carrick DJ Beck 2001 Survival and induction of SOS in Escherichia coli treated with cisplatin, UV-irradiation, or mitomycin C are dependent on the function of the RecBC and RecFOR pathways of homologous recombination Mutat Res 486 21 29 11356333
7. AA Sartori C Lukas J Coates M Mistrik S Fu J Bartek R Baer J Lukas SP Jackson 2007 Human CtIP promotes DNA end resection Nature 450 509 514 17965729
8. Huertas P. DNA resection in eukaryotes: deciding how to fix the break. Nat Struct Mol Biol 17:11-16
9. Y Wu T Sugiyama SC Kowalczykowski 2006 DNA annealing mediated by Rad52 and Rad59 proteins J Biol Chem 281 15441 15449 16565518
10. MI Petalcorin J Sandall DB Wigley SJ Boulton 2006 CeBRCA-2 stimulates D-loop formation by RAD-51 and promotes DNA single-strand annealing J Mol Biol 361 231 242 16843491
11. N Liu JE Lamerdin RS Tebbs D Schild JD Tucker MR Shen KW Brookman MJ Siciliano CA Walter W Fan LS Narayana ZQ Zhou AW Adamson KJ Sorensen DJ Chen NJ Jones LH Thompson 1998 XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages Mol Cell 1 783 793 9660962
12. E Sonoda GY Zhao M Kohzaki PK Dhar K Kikuchi C Redon DR Pilch WM Bonner A Nakano M Watanabe T Nakayama S Takeda Y Takami 2007 Collaborative roles of gammaH2AX and the Rad51 paralog Xrcc3 in homologous recombinational repair DNA Repair (Amst) 6 280 292
13. M Tarsounas D Davies SC West 2003 BRCA2-dependent and independent formation of RAD51 nuclear foci Oncogene 22 1115 1123 12606939
14. MJ McIlwraith A Vaisman Y Liu E Fanning R Woodgate SC West 2005 Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination Mol Cell 20 783 792 16337601
15. PM Burgers 2009 Polymerase dynamics at the eukaryotic DNA replication fork J Biol Chem 284 4041 4045 18835809
16. SC Ip U Rass MG Blanco HR Flynn JM Skehel SC West 2008 Identification of Holliday junction resolvases from humans and yeast Nature 456 357 361 19020614
17. EP Mimitou LS Symington 2009 Nucleases and helicases take center stage in homologous recombination Trends Biochem Sci 34 264 272 19375328
18. JA Kaye JA Melo SK Cheung MB Vaze JE Haber DP Toczyski 2004 DNA breaks promote genomic instability by impeding proper chromosome segregation Curr Biol 14 2096 2106 15589151
19. JM Stark M Jasin 2003 Extensive loss of heterozygosity is suppressed during homologous repair of chromosomal breaks Mol Cell Biol 23 733 743 12509470
20. EL Ivanov N Sugawara J Fishman-Lobell JE Haber 1996 Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae Genetics 142 693 704 8849880
21. MR Lieber 2008 The mechanism of human nonhomologous DNA end joining J Biol Chem 283 1 5 17999957
22. MR Lieber K Yu SC Raghavan 2006 Roles of nonhomologous DNA end joining, V(D)J recombination, and class switch recombination in chromosomal translocations DNA Repair (Amst) 5 1234 1245
23. MR Lieber Y Ma U Pannicke K Schwarz 2003 Mechanism and regulation of human non-homologous DNA end-joining Nat Rev Mol Cell Biol 4 712 720 14506474
24. E Riballo M Kuhne N Rief A Doherty GC Smith MJ Recio C Reis K Dahm A Fricke A Krempler AR Parker SP Jackson A Gennery PA Jeggo M Lobrich 2004 A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci Mol Cell 16 715 724 15574327
25. AA Goodarzi AT Noon D Deckbar Y Ziv Y Shiloh M Lobrich PA Jeggo 2008 ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin Mol Cell 31 167 177 18657500
26. JR Walker RA Corpina J Goldberg 2001 Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair Nature 412 607 614 11493912
27. M Falzon JW Fewell EL Kuff 1993 EBP-80, a transcription factor closely resembling the human autoantigen Ku, recognizes single- to double-strand transitions in DNA J Biol Chem 268 10546 10552 8486707
28. TM Gottlieb SP Jackson 1993 The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen Cell 72 131 142 8422676
29. T Mimori JA Hardin 1986 Mechanism of interaction between Ku protein and DNA J Biol Chem 261 10375 10379 3015926
30. P Calsou P Frit O Humbert C Muller DJ Chen B Salles 1999 The DNA-dependent protein kinase catalytic activity regulates DNA end processing by means of Ku entry into DNA J Biol Chem 274 7848 7856 10075677
31. BK Singleton MI Torres-Arzayus ST Rottinghaus GE Taccioli PA Jeggo 1999 The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit Mol Cell Biol 19 3267 3277 10207052
32. SP Lees-Miller YR Chen CW Anderson 1990 Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen Mol Cell Biol 10 6472 6481 2247067
33. Y Ma U Pannicke K Schwarz MR Lieber 2002 Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination Cell 108 781 794 11955432
34. M Yaneva T Kowalewski MR Lieber 1997 Interaction of DNA-dependent protein kinase with DNA and with Ku: biochemical and atomic-force microscopy studies EMBO J 16 5098 5112 9305651
35. LG DeFazio RM Stansel JD Griffith G Chu 2002 Synapsis of DNA ends by DNA-dependent protein kinase EMBO J 21 3192 3200 12065431
36. L Chen K Trujillo P Sung AE Tomkinson 2000 Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase J Biol Chem 275 26196 26205 10854421
37. M Lobrich PA Jeggo 2005 The two edges of the ATM sword: co-operation between repair and checkpoint functions Radiother Oncol 76 112 118 16026874
38. C Chappell LA Hanakahi F Karimi-Busheri M Weinfeld SC West 2002 Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining EMBO J 21 2827 2832 12032095
39. X Wu TE Wilson MR Lieber 1999 A role for FEN-1 in nonhomologous DNA end joining: the order of strand annealing and nucleolytic processing events Proc Natl Acad Sci USA 96 1303 1308 9990019
40. Y Ma H Lu B Tippin MF Goodman N Shimazaki O Koiwai CL Hsieh K Schwarz MR Lieber 2004 A biochemically defined system for mammalian nonhomologous DNA end joining Mol Cell 16 701 713 15574326
41. DB Roth TN Porter JH Wilson 1985 Mechanisms of nonhomologous recombination in mammalian cells Mol Cell Biol 5 2599 2607 3016509
42. DB Roth JH Wilson 1986 Nonhomologous recombination in mammalian cells: role for short sequence homologies in the joining reaction Mol Cell Biol 6 4295 4304 3025650
43. P Ahnesorg P Smith SP Jackson 2006 XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining Cell 124 301 313 16439205
44. A Nussenzweig MC Nussenzweig 2007 A backup DNA repair pathway moves to the forefront Cell 131 223 225 17956720
45. G Iliakis 2009 Backup pathways of NHEJ in cells of higher eukaryotes: cell cycle dependence Radiother Oncol 92 310 315 19604590
46. M Jankovic A Nussenzweig MC Nussenzweig 2007 Antigen receptor diversification and chromosome translocations Nat Immunol 8 801 808 17641661
47. MJ Difilippantonio J Zhu HT Chen E Meffre MC Nussenzweig EE Max T Ried A Nussenzweig 2000 DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation Nature 404 510 514 10761921
48. C Zhu KD Mills DO Ferguson C Lee J Manis J Fleming Y Gao CC Morton FW Alt 2002 Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations Cell 109 811 821 12110179
49. MA Bogue C Wang C Zhu DB Roth 1997 V(D)J recombination in Ku86-deficient mice: distinct effects on coding, signal, and hybrid joint formation Immunity 7 37 47 9252118
50. B Corneo RL Wendland L Deriano X Cui IA Klein SY Wong S Arnal AJ Holub GR Weller BA Pancake S Shah VL Brandt K Meek DB Roth 2007 Rag mutations reveal robust alternative end joining Nature 449 483 486 17898768
51. P Soulas-Sprauel P Rivera-Munoz L Malivert G Le Guyader V Abramowski P Revy JP de Villartay 2007 V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining Oncogene 26 7780 7791 18066091
52. CT Yan C Boboila EK Souza S Franco TR Hickernell M Murphy S Gumaste M Geyer AA Zarrin JP Manis K Rajewsky FW Alt 2007 IgH class switching and translocations use a robust non-classical end-joining pathway Nature 449 478 482 17713479
53. M Audebert B Salles P Calsou 2008 Effect of double-strand break DNA sequence on the PARP-1 NHEJ pathway Biochem Biophys Res Commun 369 982 988 18054777
54. M Wang W Wu B Rosidi L Zhang H Wang G Iliakis 2006 PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways Nucleic Acids Res 34 6170 6182 17088286
55. A Sallmyr AE Tomkinson FV Rassool 2008 Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks Blood 112 1413 1423 18524993
56. L Deriano TH Stracker A Baker JH Petrini DB Roth 2009 Roles for NBS1 in alternative nonhomologous end-joining of V(D)J recombination intermediates Mol Cell 34 13 25 19362533
57. H Wang B Rosidi R Perrault M Wang L Zhang F Windhofer G Iliakis 2005 DNA ligase III as a candidate component of backup pathways of nonhomologous end joining Cancer Res 65 4020 4030 15899791
58. M Dinkelmann E Spehalski T Stoneham J Buis Y Wu JM Sekiguchi DO Ferguson 2009 Multiple functions of MRN in end-joining pathways during isotype class switching Nat Struct Mol Biol 16 808 813 19633670
59. A Xie A Kwok R Scully 2009 Role of mammalian Mre11 in classical and alternative nonhomologous end joining Nat Struct Mol Biol 16 814 818 19633669
60. E Rass A Grabarz I Plo J Gautier P Bertrand BS Lopez 2009 Role of Mre11 in chromosomal nonhomologous end joining in mammalian cells Nat Struct Mol Biol 16 819 824 19633668
61. P Huertas F Cortes-Ledesma AA Sartori A Aguilera SP Jackson 2008 CDK targets Sae2 to control DNA-end resection and homologous recombination Nature 455 689 692 18716619
62. J Falck J Coates SP Jackson 2005 Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage Nature 434 605 611 15758953
63. CJ Bakkenist MB Kastan 2003 DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation Nature 421 499 506 12556884
64. A Beucher J Birraux L Tchouandong O Barton A Shibata S Conrad AA Goodarzi A Krempler PA Jeggo M Lobrich 2009 ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2 EMBO J 28 3413 3427 19779458
65. M Marshall S Solomon 2007 Hereditary breast-ovarian cancer: clinical findings and medical management Plast Surg Nurs 27 124 127 17901820
66. A Knudson 2001 Alfred Knudson and his two-hit hypothesis (Interview by Ezzie Hutchinson) Lancet Oncol 2 642 645 11902557
67. C Lengauer KW Kinzler B Vogelstein 1997 Genetic instability in colorectal cancers Nature 386 623 627 9121588
68. Y Patael-Karasik M Daniely WH Gotlieb G Ben-Baruch J Schiby G Barakai B Goldman A Aviram E Friedman 2000 Comparative genomic hybridization in inherited and sporadic ovarian tumors in Israel Cancer Genet Cytogenet 121 26 32 10958937
69. ID Hickson SL Davies JL Li NC Levitt P Mohaghegh PS North L Wu 2001 Role of the Bloom's syndrome helicase in maintenance of genome stability Biochem Soc Trans 29 201 204 11356154
70. AD D'Andrea M Grompe 2003 The Fanconi anaemia/BRCA pathway Nat Rev Cancer 3 23 34 12509764
71. LJ Niedernhofer AS Lalai JH Hoeijmakers 2005 Fanconi anemia (cross)linked to DNA repair Cell 123 1191 1198 16377561
72. I Garcia-Higuera T Taniguchi S Ganesan MS Meyn C Timmers J Hejna M Grompe AD D'Andrea 2001 Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway Mol Cell 7 249 262 11239454
73. L Wu ID Hickson 2006 DNA helicases required for homologous recombination and repair of damaged replication forks Annu Rev Genet 40 279 306 16856806
74. AR Meetei S Sechi M Wallisch D Yang MK Young H Joenje ME Hoatlin W Wang 2003 A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome Mol Cell Biol 23 3417 3426 12724401
75. N McCabe NC Turner CJ Lord K Kluzek A Bialkowska S Swift S Giavara MJ O'Connor AN Tutt MZ Zdzienicka GC Smith A Ashworth 2006 Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition Cancer Res 66 8109 8115 16912188
76. A Tutt D Bertwistle J Valentine A Gabriel S Swift G Ross C Griffin J Thacker A Ashworth 2001 Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences EMBO J 20 4704 4716 11532935
77. F Xia DG Taghian JS DeFrank ZC Zeng H Willers G Iliakis SN Powell 2001 Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining Proc Natl Acad Sci USA 98 8644 8649 11447276
78. ME Moynahan AJ Pierce M Jasin 2001 BRCA2 is required for homology-directed repair of chromosomal breaks Mol Cell 7 263 272 11239455
79. ME Moynahan JW Chiu BH Koller M Jasin 1999 Brca1 controls homology-directed DNA repair Mol Cell 4 511 518 10549283
80. G Nagaraju R Scully 2007 Minding the gap: the underground functions of BRCA1 and BRCA2 at stalled replication forks DNA Repair (Amst) 6 1018 1031
81. RW Martin BJ Orelli M Yamazoe AJ Minn S Takeda DK Bishop 2007 RAD51 up-regulation bypasses BRCA1 function and is a common feature of BRCA1-deficient breast tumors Cancer Res 67 9658 9665 17942895
82. Z Mao Y Jiang X Liu A Seluanov V Gorbunova 2009 DNA repair by homologous recombination, but not by nonhomologous end joining, is elevated in breast cancer cells Neoplasia 11 683 691 19568413
83. E Raderschall K Stout S Freier V Suckow S Schweiger T Haaf 2002 Elevated levels of Rad51 recombination protein in tumor cells Cancer Res 62 219 225 11782381
84. RS Bindra PJ Schaffer A Meng J Woo K Maseide ME Roth P Lizardi DW Hedley RG Bristow PM Glazer 2004 Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells Mol Cell Biol 24 8504 8518 15367671
85. H Willers AG Taghian CM Luo A Treszezamsky DC Sgroi SN Powell 2009 Utility of DNA repair protein foci for the detection of putative BRCA1 pathway defects in breast cancer biopsies Mol Cancer Res 7 1304 1309 19671671
86. DO Ferguson JM Sekiguchi S Chang KM Frank Y Gao RA DePinho FW Alt 2000 The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations Proc Natl Acad Sci USA 97 6630 6633 10823907
87. A Kurimasa H Ouyang LJ Dong S Wang X Li C Cordon-Cardo DJ Chen GC Li 1999 Catalytic subunit of DNA-dependent protein kinase: impact on lymphocyte development and tumorigenesis Proc Natl Acad Sci USA 96 1403 1408 9990036 (Pubitemid 29098463)
88. GC Li H Ouyang X Li H Nagasawa JB Little DJ Chen CC Ling Z Fuks C Cordon-Cardo 1998 Ku70: a candidate tumor suppressor gene for murine T cell lymphoma Mol Cell 2 1 8 9702186
89. F Lovisa L Mussolin L Corral M Pillon G Cazzaniga A Biondi A Rosolen 2009 IGH and IGK gene rearrangements as PCR targets for pediatric Burkitt's lymphoma and mature B-ALL MRD analysis Lab Invest 89 1182 1186 19668242
90. Y Gao DO Ferguson W Xie JP Manis J Sekiguchi KM Frank J Chaudhuri J Horner RA DePinho FW Alt 2000 Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development Nature 404 897 900 10786799
91. NE Sharpless DO Ferguson RC O'Hagan DH Castrillon C Lee PA Farazi S Alson J Fleming CC Morton K Frank L Chin FW Alt RA DePinho 2001 Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions Mol Cell 8 1187 1196 11779495
92. E Riballo SE Critchlow SH Teo AJ Doherty A Priestley B Broughton B Kysela H Beamish N Plowman CF Arlett AR Lehmann SP Jackson PA Jeggo 1999 Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient Curr Biol 9 699 702 10395545
93. M O'Driscoll KM Cerosaletti PM Girard Y Dai M Stumm B Kysela B Hirsch A Gennery SE Palmer J Seidel RA Gatti R Varon MA Oettinger H Neitzel PA Jeggo P Concannon 2001 DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency Mol Cell 8 1175 1185 11779494
94. J Andreae R Varon K Sperling K Seeger 2007 Polymorphisms in the DNA ligase IV gene might influence the risk of acute lymphoblastic leukemia in children Leukemia 21 2226 2227 17541392
95. X Chen S Zhong X Zhu B Dziegielewska T Ellenberger GM Wilson AD MacKerell Jr AE Tomkinson 2008 Rational design of human DNA ligase inhibitors that target cellular DNA replication and repair Cancer Res 68 3169 3177 18451142
96. N Brady TJ Gaymes M Cheung GJ Mufti FV Rassool 2003 Increased error-prone NHEJ activity in myeloid leukemias is associated with DNA damage at sites that recruit key nonhomologous end-joining proteins Cancer Res 63 1798 1805 12702565
97. MR,F Nowicki M Koptyra A Slupianek T Stoklosa E Gloc M Nieborowska-Skorska J Blasiak T Skorski 2004 BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double strand breaks Blood 104 3746 3753 15304390
98. TJ Gaymes GJ Mufti FV Rassool 2002 Myeloid leukemias have increased activity of the nonhomologous end-joining pathway and concomitant DNA misrepair that is dependent on the Ku70/86 heterodimer Cancer Res 62 2791 2797 12019155
99. Friedberg EC, Walker EH, Siede W (1995) DNA repair and mutagenesis. ASM press, Washington, DC
100. JN Sarkaria EC Busby RS Tibbetts P Roos Y Taya LM Karnitz RT Abraham 1999 Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine Cancer Res 59 4375 4382 10485486
101. I Hickson Y Zhao CJ Richardson SJ Green NM Martin AI Orr PM Reaper SP Jackson NJ Curtin GC Smith 2004 Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM Cancer Res 64 9152 9159 15604286
102. RD Kennedy CC Chen P Stuckert EM Archila MA De la Vega LA Moreau A Shimamura AD D'Andrea 2007 Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated J Clin Invest 117 1440 1449 17431503
103. CM Hine A Seluanov V Gorbunova 2008 Use of the Rad51 promoter for targeted anti-cancer therapy Proc Natl Acad Sci USA 105 20810 20815 19106292
104. T Ohnishi T Taki S Hiraga N Arita T Morita 1998 In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by antisense inhibition of the RAD51 gene Biochem Biophys Res Commun 245 319 324 9571148
105. A Husain G He ES Venkatraman DR Spriggs 1998 BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II) Cancer Res 58 1120 1123 9515792
106. A Dupre L Boyer-Chatenet RM Sattler AP Modi JH Lee ML Nicolette L Kopelovich M Jasin R Baer TT Paull J Gautier 2008 A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex Nat Chem Biol 4 119 125 18176557
107. SN Powell LA Kachnic 2008 Therapeutic exploitation of tumor cell defects in homologous recombination Anticancer Agents Med Chem 8 448 460 18473729
108. J Markowitz I Chen R Gitti DM Baldisseri Y Pan R Udan F Carrier AD MacKerell Jr DJ Weber 2004 Identification and characterization of small molecule inhibitors of the calcium-dependent S100B-p53 tumor suppressor interaction J Med Chem 47 5085 5093 15456252
109. JC Ame C Spenlehauer G de Murcia 2004 The PARP superfamily Bioessays 26 882 893 15273990
110. S Okano L Lan KW Caldecott T Mori A Yasui 2003 Spatial and temporal cellular responses to single-strand breaks in human cells Mol Cell Biol 23 3974 3981 12748298
111. J Menissier de Murcia M Ricoul L Tartier C Niedergang A Huber F Dantzer V Schreiber JC Ame A Dierich M LeMeur L Sabatier P Chambon G de Murcia 2003 Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse EMBO J 22 2255 2263 12727891
112. HE Bryant N Schultz HD Thomas KM Parker D Flower E Lopez S Kyle M Meuth NJ Curtin T Helleday 2005 Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase Nature 434 913 917 15829966
113. H Farmer N McCabe CJ Lord AN Tutt DA Johnson TB Richardson M Santarosa KJ Dillon I Hickson C Knights NM Martin SP Jackson GC Smith A Ashworth 2005 Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature 434 917 921 15829967
114. L Tentori C Leonetti M Scarsella G d'Amati I Portarena G Zupi E Bonmassar G Graziani 2002 Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site Blood 99 2241 2244 11877304
115. SK Liu C Coackley M Krause F Jalali N Chan RG Bristow 2008 A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia Radiother Oncol 88 258 268 18456354
116. CJ Lord A Ashworth 2008 Targeted therapy for cancer using PARP inhibitors Curr Opin Pharmacol 8 363 369 18644251
117. B Evers R Drost E Schut M de Bruin E van der Burg PW Derksen H Holstege X Liu E van Drunen HB Beverloo GC Smith NM Martin A Lau MJ O'Connor J Jonkers 2008 Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin Clin Cancer Res 14 3916 3925 18559613
118. PC Fong DS Boss TA Yap A Tutt P Wu M Mergui-Roelvink P Mortimer H Swaisland A Lau MJ O'Connor A Ashworth J Carmichael SB Kaye JH Schellens JS de Bono 2009 Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers N Engl J Med 361 123 134 19553641
119. Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, De Greve J, Lubinski J, Shanley S, Messiou C, A'Hern R, Tutt A, Ashworth A, Stone J, Carmichael J, Schellens JH, de Bono JS, Kaye SB. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol 28:2510-2519
120. H Wang X Wang P Zhang Y Wang 2008 The Ku-dependent non-homologous end-joining but not other repair pathway is inhibited by high linear energy transfer ionizing radiation DNA Repair (Amst) 7 725 733
121. A Eriksson R Lewensohn A Nilsson 2000 Expression and activity of DNA-dependent protein kinase in normal human leukocytes Anticancer Res 20 3051 3058 11062722
122. U Grawunder N Finnie SP Jackson B Riwar R Jessberger 1996 Expression of DNA-dependent protein kinase holoenzyme upon induction of lymphocyte differentiation and V(D)J recombination Eur J Biochem 241 931 940 8944785
123. K Okaichi K Suzuki N Morita M Ikeda H Takahashi N Matsuda M Watanabe Y Okumura 2002 Low dose of wortmannin reduces radiosensitivity of human glioblastoma cells through the p53 pathway Oncol Rep 9 859 862 12066222
124. ET Shinohara L Geng J Tan H Chen Y Shir E Edwards J Halbrook EA Kesicki A Kashishian DE Hallahan 2005 DNA-dependent protein kinase is a molecular target for the development of noncytotoxic radiation-sensitizing drugs Cancer Res 65 4987 4992 15958537
125. KE Rosenzweig MB Youmell ST Palayoor BD Price 1997 Radiosensitization of human tumor cells by the phosphatidylinositol3-kinase inhibitors wortmannin and LY294002 correlates with inhibition of DNA-dependent protein kinase and prolonged G2-M delay Clin Cancer Res 3 1149 1156 9815794
126. T Ellenberger AE Tomkinson 2008 Eukaryotic DNA ligases: structural and functional insights Annu Rev Biochem 77 313 338 18518823
127. S Zhong X Chen X Zhu B Dziegielewska KE Bachman T Ellenberger JD Ballin GM Wilson AE Tomkinson AD Mackerell Jr 2008 Identification and validation of human DNA ligase inhibitors using computer-aided drug design J Med Chem 51 4553 4562 18630893
128. S Vijayakumar B Dziegielewska DS Levin W Song J Yin A Yang Y Matsumoto VP Bermudez J Hurwitz AE Tomkinson 2009 Phosphorylation of human DNA ligase I regulates its interaction with replication factor C and its participation in DNA replication and DNA repair Mol Cell Biol 29 2042 2052 19223468
129. U Lakshmipathy C Campbell 2001 Antisense-mediated decrease in DNA ligase III expression results in reduced mitochondrial DNA integrity Nucleic Acids Res 29 668 676 11160888