DNA double-strand break repair inhibitors as cancer therapeutics

Chemistry and Biology

Volumn 22, Issue 1, 2015, Pages 17-29

  Srivastava, Mrinal ^a   Raghavan, Sathees C ^a  

^a INDIAN INSTITUTE OF SCIENCE   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; DOUBLE STRANDED DNA; ENZYME INHIBITOR; RECOMBINASE; TUMOR SUPPRESSOR PROTEIN;

CANCER RESISTANCE; CANCER THERAPY; DNA REPAIR; DNA SYNTHESIS INHIBITION; GENE ACTIVATION; GENE TARGETING; HOMOLOGOUS RECOMBINATION; PRIORITY JOURNAL; REVIEW; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; DRUG RESISTANCE; GENETIC RECOMBINATION; GENETICS; HUMAN; METABOLISM; NEOPLASMS; PATHOLOGY;

EUKARYOTA;

ANTINEOPLASTIC AGENTS; DNA REPAIR; DRUG RESISTANCE, NEOPLASM; ENZYME INHIBITORS; HUMANS; NEOPLASMS; RECOMBINASES; RECOMBINATION, GENETIC; TUMOR SUPPRESSOR PROTEINS;

EID: 84921534030     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2014.11.013     Document Type: Review

References (171)

1. M. Aggarwal, J.A. Sommers, R.H. Shoemaker, and R.M. Brosh Jr. Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress Proc. Natl. Acad. Sci. USA 108 2011 1525 1530
2. A. Ahmad, A.R. Robinson, A. Duensing, E. van Drunen, H.B. Beverloo, D.B. Weisberg, P. Hasty, J.H. Hoeijmakers, and L.J. Niedernhofer ERCC1-XPF endonuclease facilitates DNA double-strand break repair Mol. Cell. Biol. 28 2008 5082 5092
3. A. Arai, T. Chano, K. Futami, Y. Furuichi, K. Ikebuchi, T. Inui, H. Tameno, Y. Ochi, T. Shimada, Y. Hisa, and H. Okabe RECQL1 and WRN proteins are potential therapeutic targets in head and neck squamous cell carcinoma Cancer Res. 71 2011 4598 4607
4. I.S. Ayene, L.P. Ford, and C.J. Koch Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase II inhibitor and gamma radiation Mol. Cancer Ther. 4 2005 529 536
5. C. Barlow, S. Hirotsune, R. Paylor, M. Liyanage, M. Eckhaus, F. Collins, Y. Shiloh, J.N. Crawley, T. Ried, D. Tagle, and A. Wynshaw-Boris Atm-deficient mice: a paradigm of ataxia telangiectasia Cell 86 1996 159 171
6. D.E. Barnes, G. Stamp, I. Rosewell, A. Denzel, and T. Lindahl Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice Curr. Biol. 8 1998 1395 1398
7. A.C. Begg, F.A. Stewart, and C. Vens Strategies to improve radiotherapy with targeted drugs Nat. Rev. Cancer 11 2011 239 253
8. A.I. Belenkov, J.P. Paiement, L.C. Panasci, B.P. Monia, and T.Y. Chow An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents Cancer Res. 62 2002 5888 5896
9. B. Bertocci, A. De Smet, J.C. Weill, and C.A. Reynaud Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo Immunity 25 2006 31 41
10. C. Beskow, J. Skikuniene, A. Holgersson, B. Nilsson, R. Lewensohn, L. Kanter, and K. Viktorsson Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86 Br. J. Cancer 101 2009 816 821
11. C. Boboila, C. Yan, D.R. Wesemann, M. Jankovic, J.H. Wang, J. Manis, A. Nussenzweig, M. Nussenzweig, and F.W. Alt Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4 J. Exp. Med. 207 2010 417 427
12. M.N. Boddy, P.H. Gaillard, W.H. McDonald, P. Shanahan, J.R. Yates 3rd, and P. Russell Mus81-Eme1 are essential components of a Holliday junction resolvase Cell 107 2001 537 548
13. D. Branzei, and M. Foiani Regulation of DNA repair throughout the cell cycle Nat. Rev. Mol. Cell Biol. 9 2008 297 308
14. J.C. Brenner, B. Ateeq, Y. Li, A.K. Yocum, Q. Cao, I.A. Asangani, S. Patel, X. Wang, H. Liang, and J. Yu Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer Cancer Cell 19 2011 664 678
15. E.J. Brown, and D. Baltimore ATR disruption leads to chromosomal fragmentation and early embryonic lethality Genes Dev. 14 2000 397 402
16. M. Bryans, M.C. Valenzano, and T.D. Stamato Absence of DNA ligase IV protein in XR-1 cells: evidence for stabilization by XRCC4 Mutat. Res. 433 1999 53 58
17. H.E. Bryant, N. Schultz, H.D. Thomas, K.M. Parker, D. Flower, E. Lopez, S. Kyle, M. Meuth, N.J. Curtin, and T. Helleday Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase Nature 434 2005 913 917
18. B. Budke, H.L. Logan, J.H. Kalin, A.S. Zelivianskaia, W. Cameron McGuire, L.L. Miller, J.M. Stark, A.P. Kozikowski, D.K. Bishop, and P.P. Connell RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells Nucleic Acids Res. 40 2012 7347 7357
19. B. Budke, J.H. Kalin, M. Pawlowski, A.S. Zelivianskaia, M. Wu, A.P. Kozikowski, and P.P. Connell An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity J. Med. Chem. 56 2013 254 263
20. J. Budman, S.A. Kim, and G. Chu Processing of DNA for nonhomologous end-joining is controlled by kinase activity and XRCC4/ligase IV J. Biol. Chem. 282 2007 11950 11959
21. A. Carreira, and S.C. Kowalczykowski Two classes of BRC repeats in BRCA2 promote RAD51 nucleoprotein filament function by distinct mechanisms Proc. Natl. Acad. Sci. USA 108 2011 10448 10453
22. T. Carter, I. Vancurová, I. Sun, W. Lou, and S. DeLeon A DNA-activated protein kinase from HeLa cell nuclei Mol. Cell. Biol. 10 1990 6460 6471
23. J.F. Carvalho, and R. Kanaar Targeting homologous recombination-mediated DNA repair in cancer Expert Opin. Ther. Targets 18 2014 427 458
24. J.R. Chapman, P. Barral, J.B. Vannier, V. Borel, M. Steger, A. Tomas-Loba, A.A. Sartori, I.R. Adams, F.D. Batista, and S.J. Boulton RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection Mol. Cell 49 2013 858 871
25. X. Chen, S. Zhong, X. Zhu, B. Dziegielewska, T. Ellenberger, G.M. Wilson, A.D. MacKerell Jr., and A.E. Tomkinson Rational design of human DNA ligase inhibitors that target cellular DNA replication and repair Cancer Res. 68 2008 3169 3177
26. H. Chen, M. Lisby, and L.S. Symington RPA coordinates DNA end resection and prevents formation of DNA hairpins Mol. Cell 50 2013 589 600
27. B. Corneo, R.L. Wendland, L. Deriano, X. Cui, I.A. Klein, S.-Y. Wong, S. Arnal, A.J. Holub, G.R. Weller, and B.A. Pancake Rag mutations reveal robust alternative end joining Nature 449 2007 483 486
28. D. Cortez Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases J. Biol. Chem. 278 2003 37139 37145
29. S.E. Critchlow, R.P. Bowater, and S.P. Jackson Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV Curr. Biol. 7 1997 588 598
30. N.J. Curtin DNA repair dysregulation from cancer driver to therapeutic target Nat. Rev. Cancer 12 2012 801 817
31. F. d'Adda di Fagagna, M.P. Hande, W.M. Tong, D. Roth, P.M. Lansdorp, Z.Q. Wang, and S.P. Jackson Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells Curr. Biol. 11 2001 1192 1196
32. J.M. Darbon, M. Penary, N. Escalas, F. Casagrande, F. Goubin-Gramatica, C. Baudouin, and B. Ducommun Distinct Chk2 activation pathways are triggered by genistein and DNA-damaging agents in human melanoma cells J. Biol. Chem. 275 2000 15363 15369
33. J.S. Deakyne, F. Huang, J. Negri, N. Tolliday, S. Cocklin, and A.V. Mazin Analysis of the activities of RAD54, a SWI2/SNF2 protein, using a specific small-molecule inhibitor J. Biol. Chem. 288 2013 31567 31580
34. J. Della-Maria, Y. Zhou, M.S. Tsai, J. Kuhnlein, J. Carney, T. Paull, and A. Tomkinson Human Mre11/human Rad50/Nbs1 and DNA ligase IIIalpha/XRCC1 protein complexes act together in an alternative nonhomologous end joining pathway J. Biol. Chem. 286 2011 33845 33853
35. K.K. Dhillon, E.M. Swisher, and T. Taniguchi Secondary mutations of BRCA1/2 and drug resistance Cancer Sci. 102 2011 663 669
36. J.A. Downs, and S.P. Jackson A means to a DNA end: the many roles of Ku Nat. Rev. Mol. Cell Biol. 5 2004 367 378
37. A. Dupré, L. Boyer-Chatenet, R.M. Sattler, A.P. Modi, J.H. Lee, M.L. Nicolette, L. Kopelovich, M. Jasin, R. Baer, T.T. Paull, and J. Gautier A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex Nat. Chem. Biol. 4 2008 119 125
38. T. Ellenberger, and A.E. Tomkinson Eukaryotic DNA ligases: structural and functional insights Annu. Rev. Biochem. 77 2008 313 338
39. J. Essers, R.W. Hendriks, S.M. Swagemakers, C. Troelstra, J. de Wit, D. Bootsma, J.H. Hoeijmakers, and R. Kanaar Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination Cell 89 1997 195 204
40. B. Evers, and J. Jonkers Mouse models of BRCA1 and BRCA2 deficiency: past lessons, current understanding and future prospects Oncogene 25 2006 5885 5897
41. H. Farmer, N. McCabe, C.J. Lord, A.N. Tutt, D.A. Johnson, T.B. Richardson, M. Santarosa, K.J. Dillon, I. Hickson, and C. Knights Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature 434 2005 917 921
42. F. Fattah, E.H. Lee, N. Weisensel, Y. Wang, N. Lichter, and E.A. Hendrickson Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells PLoS Genet. 6 2010 e1000855
43. Z. Feng, S.P. Scott, W. Bussen, G.G. Sharma, G. Guo, T.K. Pandita, and S.N. Powell Rad52 inactivation is synthetically lethal with BRCA2 deficiency Proc. Natl. Acad. Sci. USA 108 2011 686 691
44. K.M. Frank, N.E. Sharpless, Y. Gao, J.M. Sekiguchi, D.O. Ferguson, C. Zhu, J.P. Manis, J. Horner, R.A. DePinho, and F.W. Alt DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway Mol. Cell 5 2000 993 1002
45. W.M. Fricke, and S.J. Brill Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3 Genes Dev. 17 2003 1768 1778
46. P. Frit, Y. Canitrot, C. Muller, N. Foray, P. Calsou, E. Marangoni, J. Bourhis, and B. Salles Cross-resistance to ionizing radiation in a murine leukemic cell line resistant to cis-dichlorodiammineplatinum(II): role of Ku autoantigen Mol. Pharmacol. 56 1999 141 146
47. H. Gad, T. Koolmeister, A.S. Jemth, S. Eshtad, S.A. Jacques, C.E. Ström, L.M. Svensson, N. Schultz, T. Lundbäck, and B.O. Einarsdottir MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool Nature 508 2014 215 221
48. Y. Gao, D.O. Ferguson, W. Xie, J.P. Manis, J. Sekiguchi, K.M. Frank, J. Chaudhuri, J. Horner, R.A. DePinho, and F.W. Alt Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development Nature 404 2000 897 900
49. M. Gostissa, F.W. Alt, and R. Chiarle Mechanisms that promote and suppress chromosomal translocations in lymphocytes Annu. Rev. Immunol. 29 2011 319 350
50. U. Grawunder, M. Wilm, X. Wu, P. Kulesza, T.E. Wilson, M. Mann, and M.R. Lieber Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells Nature 388 1997 492 495
51. U. Grawunder, D. Zimmer, and M.R. Lieber DNA ligase IV binds to XRCC4 via a motif located between rather than within its BRCT domains Curr. Biol. 8 1998 873 876
52. S.B. Gruber, N.A. Ellis, K.K. Scott, R. Almog, P. Kolachana, J.D. Bonner, T. Kirchhoff, L.P. Tomsho, K. Nafa, and H. Pierce BLM heterozygosity and the risk of colorectal cancer Science 297 2002 2013
53. J. Gu, H. Lu, B. Tippin, N. Shimazaki, M.F. Goodman, and M.R. Lieber XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps EMBO J. 26 2007 1010 1023
54. R. Gupta, and R.M. Brosh Jr. Helicases as prospective targets for anti-cancer therapy Anticancer. Agents Med. Chem. 8 2008 390 401
55. J.A. Hannay, J. Liu, Q.S. Zhu, S.V. Bolshakov, L. Li, P.W. Pisters, A.J. Lazar, D. Yu, R.E. Pollock, and D. Lev Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation Mol. Cancer Ther. 6 2007 1650 1660
56. L.T. Hansen, C. Lundin, M. Spang-Thomsen, L.N. Petersen, and T. Helleday The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer Int. J. Cancer 105 2003 472 479
57. T. Helleday Homologous recombination in cancer development, treatment and development of drug resistance Carcinogenesis 31 2010 955 960
58. I. Hickson, Y. Zhao, C.J. Richardson, S.J. Green, N.M. Martin, A.I. Orr, P.M. Reaper, S.P. Jackson, N.J. Curtin, and G.C. Smith Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM Cancer Res. 64 2004 9152 9159
59. H.L. Hsu, D. Gilley, E.H. Blackburn, and D.J. Chen Ku is associated with the telomere in mammals Proc. Natl. Acad. Sci. USA 96 1999 12454 12458
60. F. Huang, N.A. Motlekar, C.M. Burgwin, A.D. Napper, S.L. Diamond, and A.V. Mazin Identification of specific inhibitors of human RAD51 recombinase using high-throughput screening ACS Chem. Biol. 6 2011 628 635
61. K.V. Huber, E. Salah, B. Radic, M. Gridling, J.M. Elkins, A. Stukalov, A.S. Jemth, C. Göktürk, K. Sanjiv, and K. Strömberg Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy Nature 508 2014 222 227
62. D. Hussein, W. Punjaruk, L.C. Storer, L. Shaw, R. Othman, A. Peet, S. Miller, G. Bandopadhyay, R. Heath, and R. Kumari Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion Neuro-oncol. 13 2011 70 83
63. F. Hutchinson Chemical changes induced in DNA by ionizing radiation Prog. Nucleic Acid Res. Mol. Biol. 32 1985 115 154
64. S.C. Ip, U. Rass, M.G. Blanco, H.R. Flynn, J.M. Skehel, and S.C. West Identification of Holliday junction resolvases from humans and yeast Nature 456 2008 357 361
65. P. Jeggo, B. Singleton, H. Beamish, and A. Priestley Double strand break rejoining by the Ku-dependent mechanism of non-homologous end-joining C. R. Acad. Sci. III 322 1999 109 112
66. C. Jenkins, J. Kan, and M.E. Hoatlin Targeting the fanconi anemia pathway to identify tailored anticancer therapeutics Anemia 2012 2012 481583
67. L.P. Jordheim, K.H. Barakat, L. Heinrich-Balard, E.L. Matera, E. Cros-Perrial, K. Bouledrak, R. El Sabeh, R. Perez-Pineiro, D.S. Wishart, and R. Cohen Small molecule inhibitors of ERCC1-XPF protein-protein interaction synergize alkylating agents in cancer cells Mol. Pharmacol. 84 2013 12 24
68. W.G. Kaelin Jr. The concept of synthetic lethality in the context of anticancer therapy Nat. Rev. Cancer 5 2005 689 698
69. Z.E. Karanjawala, N. Adachi, R.A. Irvine, E.K. Oh, D. Shibata, K. Schwarz, C.L. Hsieh, and M.R. Lieber The embryonic lethality in DNA ligase IV-deficient mice is rescued by deletion of Ku: implications for unifying the heterogeneous phenotypes of NHEJ mutants DNA Repair (Amst.) 1 2002 1017 1026
70. P.M. Krawczyk, B. Eppink, J. Essers, J. Stap, H. Rodermond, H. Odijk, A. Zelensky, C. van Bree, L.J. Stalpers, and M.R. Buist Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition Proc. Natl. Acad. Sci. USA 108 2011 9851 9856
71. B. Kuschel, A. Auranen, S. McBride, K.L. Novik, A. Antoniou, J.M. Lipscombe, N.E. Day, D.F. Easton, B.A. Ponder, P.D. Pharoah, and A. Dunning Variants in DNA double-strand break repair genes and breast cancer susceptibility Hum. Mol. Genet. 11 2002 1399 1407
72. M. Lee-Theilen, A.J. Matthews, D. Kelly, S. Zheng, and J. Chaudhuri CtIP promotes microhomology-mediated alternative end joining during class-switch recombination Nat. Struct. Mol. Biol. 18 2011 75 79
73. X. Li, and W.D. Heyer Homologous recombination in DNA repair and DNA damage tolerance Cell Res. 18 2008 99 113
74. X. Li, M.T. Lewis, J. Huang, C. Gutierrez, C.K. Osborne, M.F. Wu, S.G. Hilsenbeck, A. Pavlick, X. Zhang, and G.C. Chamness Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy J. Natl. Cancer Inst. 100 2008 672 679
75. J. Li, R. Ayene, K.M. Ward, E. Dayanandam, and I.S. Ayene Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells Cell Biochem. Funct. 27 2009 93 101
76. M.R. Lieber The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway Annu. Rev. Biochem. 79 2010 181 211
77. H.B. Lieberman DNA damage repair and response proteins as targets for cancer therapy Curr. Med. Chem. 15 2008 360 367
78. B.H. Lok, and S.N. Powell Molecular pathways: understanding the role of Rad52 in homologous recombination for therapeutic advancement Clin. Cancer Res. 18 2012 6400 6406
79. C.J. Lord, and A. Ashworth The DNA damage response and cancer therapy Nature 481 2012 287 294
80. G. Luo, M.S. Yao, C.F. Bender, M. Mills, A.R. Bladl, A. Bradley, and J.H. Petrini Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation Proc. Natl. Acad. Sci. USA 96 1999 7376 7381
81. Y. Ma, U. Pannicke, K. Schwarz, and M.R. Lieber Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination Cell 108 2002 781 794
82. Z. Mao, M. Bozzella, A. Seluanov, and V. Gorbunova DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells Cell Cycle 7 2008 2902 2906
83. E. Marangoni, N. Foray, M. O'Driscoll, S. Douc-Rasy, J. Bernier, J. Bourhis, and P. Jeggo A Ku80 fragment with dominant negative activity imparts a radiosensitive phenotype to CHO-K1 cells Nucleic Acids Res. 28 2000 4778 4782
84. E.M. McNeil, and D.W. Melton DNA repair endonuclease ERCC1-XPF as a novel therapeutic target to overcome chemoresistance in cancer therapy Nucleic Acids Res. 40 2012 9990 10004
85. M. McVey, and S.E. Lee MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings Trends Genet. 24 2008 529 538
86. T. Mimori, J.A. Hardin, and J.A. Steitz Characterization of the DNA-binding protein antigen Ku recognized by autoantibodies from patients with rheumatic disorders J. Biol. Chem. 261 1986 2274 2278
87. M. Modesti, J.E. Hesse, and M. Gellert DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with stimulation of DNA ligase IV activity EMBO J. 18 1999 2008 2018
88. S. Morandell, and M.B. Yaffe Exploiting synthetic lethal interactions between DNA damage signaling, checkpoint control, and p53 for targeted cancer therapy Prog. Mol. Biol. Transl. Sci. 110 2012 289 314
89. V.E. Morozov, M. Falzon, C.W. Anderson, and E.L. Kuff DNA-dependent protein kinase is activated by nicks and larger single-stranded gaps J. Biol. Chem. 269 1994 16684 16688
90. D. Moshous, I. Callebaut, R. de Chasseval, B. Corneo, M. Cavazzana-Calvo, F. Le Deist, I. Tezcan, O. Sanal, Y. Bertrand, and N. Philippe Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency Cell 105 2001 177 186
91. M. Mosor, I. Ziółkowska, M. Pernak-Schwarz, D. Januszkiewicz-Lewandowska, and J. Nowak Association of the heterozygous germline I171V mutation of the NBS1 gene with childhood acute lymphoblastic leukemia Leukemia 20 2006 1454 1456
92. M. Nambiar, and S.C. Raghavan How does DNA break during chromosomal translocations? Nucleic Acids Res. 39 2011 5813 5825
93. J.H. New, T. Sugiyama, E. Zaitseva, and S.C. Kowalczykowski Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A Nature 391 1998 407 410
94. G.H. Nguyen, T.S. Dexheimer, A.S. Rosenthal, W.K. Chu, D.K. Singh, G. Mosedale, C.Z. Bachrati, L. Schultz, M. Sakurai, and P. Savitsky A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells Chem. Biol. 20 2013 55 62
95. S.A. Nick McElhinny, and D.A. Ramsden Polymerase mu is a DNA-directed DNA/RNA polymerase Mol. Cell. Biol. 23 2003 2309 2315
96. S.A. Nick McElhinny, J.M. Havener, M. Garcia-Diaz, R. Juárez, K. Bebenek, B.L. Kee, L. Blanco, T.A. Kunkel, and D.A. Ramsden A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joining Mol. Cell 19 2005 357 366
97. A.V. Nimonkar, J. Genschel, E. Kinoshita, P. Polaczek, J.L. Campbell, C. Wyman, P. Modrich, and S.C. Kowalczykowski BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair Genes Dev. 25 2011 350 362
98. K. Nojima, H. Hochegger, A. Saberi, T. Fukushima, K. Kikuchi, M. Yoshimura, B.J. Orelli, D.K. Bishop, S. Hirano, and M. Ohzeki Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells Cancer Res. 65 2005 11704 11711
99. N.G. Oliveira, M. Castro, A.S. Rodrigues, O.M. Gil, J.M. Toscano-Rico, and J. Rueff DNA-PK inhibitor wortmannin enhances DNA damage induced by bleomycin in V79 Chinese hamster cells Teratog. Carcinog. Mutagen. 22 2002 343 351
100. M.N. Paddock, A.T. Bauman, R. Higdon, E. Kolker, S. Takeda, and A.M. Scharenberg Competition between PARP-1 and Ku70 control the decision between high-fidelity and mutagenic DNA repair DNA Repair (Amst.) 10 2011 338 343
101. B. Pardo, B. Gómez-González, and A. Aguilera DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship Cell. Mol. Life Sci. 66 2009 1039 1056
102. K. Paul, M. Wang, E. Mladenov, A. Bencsik-Theilen, T. Bednar, W. Wu, H. Arakawa, and G. Iliakis DNA ligases I and III cooperate in alternative non-homologous end-joining in vertebrates PLoS ONE 8 2013 e59505
103. T.T. Paull, and M. Gellert The 3′ to 5′ exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks Mol. Cell 1 1998 969 979
104. T.T. Paull, and M. Gellert Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex Genes Dev. 13 1999 1276 1288
105. A. Peasland, L.Z. Wang, E. Rowling, S. Kyle, T. Chen, A. Hopkins, W.A. Cliby, J. Sarkaria, G. Beale, R.J. Edmondson, and N.J. Curtin Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines Br. J. Cancer 105 2011 372 381
106. N. Petrucelli, M.B. Daly, and G.L. Feldman Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2 Genet. Med. 12 2010 245 259
107. S.N. Powell, and R.S. Bindra Targeting the DNA damage response for cancer therapy DNA Repair (Amst.) 8 2009 1153 1165
108. B.D. Price, and M.B. Youmell The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes murine fibroblasts and human tumor cells to radiation and blocks induction of p53 following DNA damage Cancer Res. 56 1996 246 250
109. S. Pucci, P. Mazzarelli, C. Rabitti, M. Giai, M. Gallucci, G. Flammia, A. Alcini, V. Altomare, and V.M. Fazio Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies Oncogene 20 2001 739 747
110. M.D. Rainey, M.E. Charlton, R.V. Stanton, and M.B. Kastan Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation Cancer Res. 68 2008 7466 7474
111. U. Rass, I. Ahel, and S.C. West Defective DNA repair and neurodegenerative disease Cell 130 2007 991 1004
112. E. Rass, A. Grabarz, I. Plo, J. Gautier, P. Bertrand, and B.S. Lopez Role of Mre11 in chromosomal nonhomologous end joining in mammalian cells Nat. Struct. Mol. Biol. 16 2009 819 824
113. E. Riballo, S.E. Critchlow, S.H. Teo, A.J. Doherty, A. Priestley, B. Broughton, B. Kysela, H. Beamish, N. Plowman, and C.F. Arlett Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient Curr. Biol. 9 1999 699 702
114. T. Rijkers, J. Van Den Ouweland, B. Morolli, A.G. Rolink, W.M. Baarends, P.P. Van Sloun, P.H. Lohman, and A. Pastink Targeted inactivation of mouse RAD52 reduces homologous recombination but not resistance to ionizing radiation Mol. Cell. Biol. 18 1998 6423 6429
115. S. Rooney, J. Sekiguchi, C. Zhu, H.L. Cheng, J. Manis, S. Whitlow, J. DeVido, D. Foy, J. Chaudhuri, D. Lombard, and F.W. Alt Leaky Scid phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice Mol. Cell 10 2002 1379 1390
116. K.E. Rosenzweig, M.B. Youmell, S.T. Palayoor, and B.D. Price 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 1997 1149 1156
117. J. San Filippo, P. Sung, and H. Klein Mechanism of eukaryotic homologous recombination Annu. Rev. Biochem. 77 2008 229 257
118. A. Sancar, L.A. Lindsey-Boltz, K. Unsal-Kaçmaz, and S. Linn Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints Annu. Rev. Biochem. 73 2004 39 85
119. A. Sassi, M. Popielarski, E. Synowiec, Z. Morawiec, and K. Wozniak BLM and RAD51 genes polymorphism and susceptibility to breast cancer Pathol. Oncol. Res. 19 2013 451 459
120. C. Seong, S. Colavito, Y. Kwon, P. Sung, and L. Krejci Regulation of Rad51 recombinase presynaptic filament assembly via interactions with the Rad52 mediator and the Srs2 anti-recombinase J. Biol. Chem. 284 2009 24363 24371
121. N. Shafee, C.R. Smith, S. Wei, Y. Kim, G.B. Mills, G.N. Hortobagyi, E.J. Stanbridge, and E.Y. Lee Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors Cancer Res. 68 2008 3243 3250
122. M. Shaheen, C. Allen, J.A. Nickoloff, and R. Hromas Synthetic lethality: exploiting the addiction of cancer to DNA repair Blood 117 2011 6074 6082
123. S. Sharma, and S.C. Raghavan Nonhomologous DNA end joining in cell-free extracts J. Nucleic Acids 2010 10.4061/2010/389129 Published online September 22, 2010
124. H. Shen, M. Schultz, G.D. Kruh, and K.D. Tew Increased expression of DNA-dependent protein kinase confers resistance to adriamycin Biochim. Biophys. Acta 1381 1998 131 138
125. A. Shibata, D. Moiani, A.S. Arvai, J. Perry, S.M. Harding, M.M. Genois, R. Maity, S. van Rossum-Fikkert, A. Kertokalio, and F. Romoli DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities Mol. Cell 53 2014 7 18
126. Y. Shiloh Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart Annu. Rev. Genet. 31 1997 635 662
127. S. Shintani, M. Mihara, C. Li, Y. Nakahara, S. Hino, K. Nakashiro, and H. Hamakawa Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma Cancer Sci. 94 2003 894 900
128. J.M. Sidorova Roles of the Werner syndrome RecQ helicase in DNA replication DNA Repair (Amst.) 7 2008 1776 1786
129. A.L. Simons, D.M. Mattson, K. Dornfeld, and D.R. Spitz Glucose deprivation-induced metabolic oxidative stress and cancer therapy J. Cancer Res. Ther. 5 Suppl 1 2009 S2 S6
130. D. Simsek, and M. Jasin Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation Nat. Struct. Mol. Biol. 17 2010 410 416
131. D. Simsek, E. Brunet, S.Y. Wong, S. Katyal, Y. Gao, P.J. McKinnon, J. Lou, L. Zhang, J. Li, and E.J. Rebar DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation PLoS Genet. 7 2011 e1002080
132. F. Sirzén, A. Nilsson, B. Zhivotovsky, and R. Lewensohn DNA-dependent protein kinase content and activity in lung carcinoma cell lines: correlation with intrinsic radiosensitivity Eur. J. Cancer 35 1999 111 116
133. J. Smith, C. Baldeyron, I. De Oliveira, M. Sala-Trepat, and D. Papadopoulo The influence of DNA double-strand break structure on end-joining in human cells Nucleic Acids Res. 29 2001 4783 4792
134. A. Smogorzewska, J. Karlseder, H. Holtgreve-Grez, A. Jauch, and T. de Lange DNA ligase IV-dependent NHEJ of deprotected mammalian telomeres in G1 and G2 Curr. Biol. 12 2002 1635 1644
135. J.A. Solinger, K. Kiianitsa, and W.D. Heyer Rad54, a Swi2/Snf2-like recombinational repair protein, disassembles Rad51:dsDNA filaments Mol. Cell 10 2002 1175 1188
136. E. Sonoda, M.S. Sasaki, J.M. Buerstedde, O. Bezzubova, A. Shinohara, H. Ogawa, M. Takata, Y. Yamaguchi-Iwai, and S. Takeda Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death EMBO J. 17 1998 598 608
137. O. Sordet, C.E. Redon, J. Guirouilh-Barbat, S. Smith, S. Solier, C. Douarre, C. Conti, A.J. Nakamura, B.B. Das, and E. Nicolas Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks EMBO Rep. 10 2009 887 893
138. M. Srivastava, M. Nambiar, S. Sharma, S.S. Karki, G. Goldsmith, M. Hegde, S. Kumar, M. Pandey, R.K. Singh, and P. Ray An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression Cell 151 2012 1474 1487
139. L.S. Symington, and J. Gautier Double-strand break end resection and repair pathway choice Annu. Rev. Genet. 45 2011 247 271
140. J.W. Szostak, T.L. Orr-Weaver, R.J. Rothstein, and F.W. Stahl The double-strand-break repair model for recombination Cell 33 1983 25 35
141. G.E. Taccioli, A.G. Amatucci, H.J. Beamish, D. Gell, X.H. Xiang, M.I. Torres Arzayus, A. Priestley, S.P. Jackson, A. Marshak Rothstein, P.A. Jeggo, and V.L. Herrera Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity Immunity 9 1998 355 366
142. T. Taniguchi, M. Tischkowitz, N. Ameziane, S.V. Hodgson, C.G. Mathew, H. Joenje, S.C. Mok, and A.D. D'Andrea Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors Nat. Med. 9 2003 568 574
143. L.I. Toledo, M. Murga, R. Zur, R. Soria, A. Rodriguez, S. Martinez, J. Oyarzabal, J. Pastor, J.R. Bischoff, and O. Fernandez-Capetillo A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations Nat. Struct. Mol. Biol. 18 2011 721 727
144. N. Tomimatsu, B. Mukherjee, M. Catherine Hardebeck, M. Ilcheva, C. Vanessa Camacho, J. Louise Harris, M. Porteus, B. Llorente, K.K. Khanna, and S. Burma Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice Nat. Commun. 5 2014 3561
145. L.N. Truong, Y. Li, L.Z. Shi, P.Y. Hwang, J. He, H. Wang, N. Razavian, M.W. Berns, and X. Wu Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells Proc. Natl. Acad. Sci. USA 110 2013 7720 7725
146. C.J. Tsai, S.A. Kim, and G. Chu Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends Proc. Natl. Acad. Sci. USA 104 2007 7851 7856
147. A. Vaezi, C.H. Feldman, and L.J. Niedernhofer ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer Pharmgenomics Pers Med 4 2011 47 63
148. K. Valerie, and L.F. Povirk Regulation and mechanisms of mammalian double-strand break repair Oncogene 22 2003 5792 5812
149. M. van der Burg, H. Ijspeert, N.S. Verkaik, T. Turul, W.W. Wiegant, K. Morotomi-Yano, P.O. Mari, I. Tezcan, D.J. Chen, and M.Z. Zdzienicka A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining J. Clin. Invest. 119 2009 91 98
150. S.J. Veuger, N.J. Curtin, C.J. Richardson, G.C. Smith, and B.W. Durkacz Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1 Cancer Res. 63 2003 6008 6015
151. H. Vogel, D.S. Lim, G. Karsenty, M. Finegold, and P. Hasty Deletion of Ku86 causes early onset of senescence in mice Proc. Natl. Acad. Sci. USA 96 1999 10770 10775
152. J.R. Walker, R.A. Corpina, and J. Goldberg Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair Nature 412 2001 607 614
153. M. Wang, W. Wu, W. Wu, B. Rosidi, L. Zhang, H. Wang, and G. Iliakis PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways Nucleic Acids Res. 34 2006 6170 6182
154. Y.F. Wei, P. Robins, K. Carter, K. Caldecott, D.J. Pappin, G.L. Yu, R.P. Wang, B.K. Shell, R.A. Nash, and P. Schär Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination Mol. Cell. Biol. 15 1995 3206 3216
155. E. Willmore, S. de Caux, N.J. Sunter, M.J. Tilby, G.H. Jackson, C.A. Austin, and B.W. Durkacz A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia Blood 103 2004 4659 4665
156. T.E. Wilson, U. Grawunder, and M.R. Lieber Yeast DNA ligase IV mediates non-homologous DNA end joining Nature 388 1997 495 498
157. L. Wu, and I.D. Hickson The Bloom's syndrome helicase suppresses crossing over during homologous recombination Nature 426 2003 870 874
158. C. Wyman, and R. Kanaar DNA double-strand break repair: all's well that ends well Annu. Rev. Genet. 40 2006 363 383
159. C. Wyman, D. Ristic, and R. Kanaar Homologous recombination-mediated double-strand break repair DNA Repair (Amst.) 3 2004 827 833
160. Y. Xiao, and D.T. Weaver Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells Nucleic Acids Res. 25 1997 2985 2991
161. A. Xie, A. Kwok, and R. Scully Role of mammalian Mre11 in classical and alternative nonhomologous end joining Nat. Struct. Mol. Biol. 16 2009 814 818
162. C.T. Yan, C. Boboila, E.K. Souza, S. Franco, T.R. Hickernell, M. Murphy, S. Gumaste, M. Geyer, A.A. Zarrin, and J.P. Manis IgH class switching and translocations use a robust non-classical end-joining pathway Nature 449 2007 478 482
163. M.H. Yang, S.Y. Chang, S.H. Chiou, C.J. Liu, C.W. Chi, P.M. Chen, S.C. Teng, and K.J. Wu Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer Oncogene 26 2007 1459 1467
164. M.H. Yun, and K. Hiom CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle Nature 459 2009 460 463
165. M. Zhang, F. Behbod, R.L. Atkinson, M.D. Landis, F. Kittrell, D. Edwards, D. Medina, A. Tsimelzon, S. Hilsenbeck, and J.E. Green Identification of tumor-initiating cells in a p53-null mouse model of breast cancer Cancer Res. 68 2008 4674 4682
166. B. Zhao, M.J. Bower, P.J. McDevitt, H. Zhao, S.T. Davis, K.O. Johanson, S.M. Green, N.O. Concha, and B.B. Zhou Structural basis for Chk1 inhibition by UCN-01 J. Biol. Chem. 277 2002 46609 46615
167. C. Zhu, M.A. Bogue, D.S. Lim, P. Hasty, and D.B. Roth Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates Cell 86 1996 379 389
168. J. Zhu, S. Petersen, L. Tessarollo, and A. Nussenzweig Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice Curr. Biol. 11 2001 105 109
169. C. Zhu, K.D. Mills, D.O. Ferguson, C. Lee, J. Manis, J. Fleming, Y. Gao, C.C. Morton, and F.W. Alt Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations Cell 109 2002 811 821
170. M. Zimmermann, and T. de Lange 53BP1: pro choice in DNA repair Trends Cell Biol. 24 2014 108 117
171. I. Ziółkowska-Suchanek, M. Mosor, M. Wierzbicka, M. Rydzanicz, M. Baranowska, and J. Nowak The MRN protein complex genes: MRE11 and RAD50 and susceptibility to head and neck cancers Mol. Cancer 12 2013 113