DNA damage response genes and the development of cancer metastasis

Radiation Research

Volumn 181, Issue 2, 2014, Pages 111-130

  Broustas, Constantinos G ^a   Lieberman, Howard B ^a  

^a Center for Radiological Research Columbia University College of Physicians and Surge New York NY 10032 ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; BRCA1 PROTEIN; BRCA2 PROTEIN; NIBRIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NUCLEOSIDE DIPHOSPHATE KINASE NM23; PROTEIN P53; PROTEIN RAD9; RAD51 PROTEIN; XRCC3 PROTEIN;

CANCER CELL; CARCINOGENESIS; CELL CYCLE CHECKPOINT; CELL CYCLE REGULATION; DNA DAMAGE; DNA DAMAGE CHECKPOINT; DNA END JOINING REPAIR; DNA SYNTHESIS; DOWN REGULATION; EXCISION REPAIR; GENE CONTROL; GENE EXPRESSION PROFILING; GENE FUNCTION; GENE MUTATION; GENETIC ASSOCIATION; GENOMIC INSTABILITY; HOMOLOGOUS RECOMBINATION; HUMAN; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; MELANOMA CELL; METASTASIS; MISMATCH REPAIR; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; TRANSLESION DNA SYNTHESIS; TUMOR GENE; TUMOR GROWTH; TUMOR SUPPRESSOR GENE; UPREGULATION;

ANIMALS; CARCINOGENESIS; CELL CYCLE CHECKPOINTS; DNA DAMAGE; DNA REPAIR; HUMANS; NEOPLASM METASTASIS; NEOPLASMS;

EID: 84896272979     PISSN: 00337587     EISSN: 19385404     Source Type: Journal    
DOI: 10.1667/RR13515.1     Document Type: Review

References (292)

1. Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 2012; 12:801-17.
2. de Boer J, Hoeijmakers JH. Nucleotide excision repair and human syndromes. Carcinogenesis 2000; 21:453-60.
3. Rustgi AK. The genetics of hereditary colon cancer. Genes Dev 2007; 21:2525-38.
4. Moshous D, Pannetier C, Chasseval RD, Deist FL, Cavazzana-Calvo M, Romana S, et. al. Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. J Clin Invest 2003; 111:381-7.
5. Roddam PL, Rollinson S, ODriscoll M, Jeggo PA, Jack A, Morgan GJ. Genetic variants of NHEJ DNA ligase IV can affect the risk of developing multiple myeloma, a tumour characterised by aberrant class switch recombination. J Med Genet 2002; 39:900-5.
6. Li ML, Greenberg RA. Links between genome integrity and BRCA1 tumor suppression. Trends Biochem Sci 2012; 37:418-24.
7. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 2008; 8:193-204.
8. Lieberman HB. DNA damage repair and response proteins as targets for cancer therapy. Curr Med Chem 2008; 15:360-7.
9. Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J. Aging and genome maintenance: lessons from the mouse? Science 2003; 299:1355-9.
10. Thompson LH, Schild D. Recombinational DNA repair and human disease. Mutat Res 2002; 509:49-78.
11. Lahtz C, Pfeifer GP. Epigenetic changes of DNA repair genes in cancer. J Mol Cell Biol 2011; 3:51-8.
12. Toyota M, Suzuki H. Epigenetic drivers of genetic alterations. Adv Genet 2010; 70:309-23.
13. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 1999; 59:793-7.
14. Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 2000; 343:1350-4.
15. Mellai M, Caldera V, Annovazzi L, Chiò A, Lanotte M, Cassoni P, et al. MGMT promoter hypermethylation in a series of 104 glioblastomas. Cancer Genomics Proteomics 2009; 6:219-27.
16. Shamsara J, Sharif S, Afsharnezhad S, Lotfi M, Raziee HR, Ghaffarzadegan K, et al. Association between MGMT promoter hypermethylation and p53 mutation in glioblastoma. Cancer Invest 2009; 27:825-9.
17. Herfarth KK, Brent TP, Danam RP, Remack JS, Kodner IJ, Wells SA, et al. A specific CpG methylation pattern of the MGMT promoter region associated with reduced MGMT expression in primary colorectal cancers. Mol Carcinog 1999; 24:90-8.
18. Ogino S, Hazra A, Tranah GJ, Kirkner GJ, Kawasaki T, Nosho K, et al. MGMT germline polymorphism is associated with somatic MGMT promoter methylation and gene silencing in colorectal cancer. Carcinogenesis 2007; 28:1985-90.
19. Wolf P, Hu YC, Doffek K, Sidransky D, Ahrendt SA. O(6)-Methylguanine-DNA methyltransferase promoter hypermethylation shifts the p53 mutational spectrum in non-small cell lung cancer. Cancer Res 2001; 61:8113-7.
20. Wu JY, Wang J, Lai JC, Cheng YW, Yeh KT, Wu TC, et al. Association of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with p53 mutation occurrence in non-small cell lung cancer with different histology, gender, and smoking status. Ann Surg Oncol 2008; 15:3272-7.
21. Oue N, Shigeishi H, Kuniyasu H, Yokozaki H, Kuraoka K, et al. Promoter hypermethylation of MGMT is associated with protein loss in gastric carcinoma. Int J Cancer 2001; 93:805-9.
22. Goldenberg D, Harden S, Masayesva BG, Ha P, Benoit N, Westra WH, et al. Intraoperative molecular margin analysis in head and neck cancer. Arch Otolaryngol Head Neck Surg 2004; 130:39-44.
23. Maruya S, Issa JP, Weber RS, Rosenthal DI, Haviland JC, Lotan R, et al. Differential methylation status of tumor-Associated genes in head and neck squamous carcinoma: incidence and potential implications. Clin Cancer Res 2004; 10:3825-30.
24. Steinmann K, Sandner A, Schagdarsurengin U, Dammann RH. Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma. Oncol Rep 2009; 22:1519-26.
25. Esteller M, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Watkins DN, et al. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis. Cancer Res 2000; 60:2368-71.
26. Esteller M, Risques RA, Toyota M, Capella G, Moreno V, Peinado MA, et al. Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis. Cancer Res 2001; 61:4689-92.
27. Dianov GL, Hübscher U. Mammalian base excision repair: the forgotten archangel. Nucleic Acids Res 2013; 41:3483-90.
28. Wilson DM 3rd, Kim D, Berquist BR, Sigurdson AJ. Variation in base excision repair capacity. Mutat Res 2011; 711:100-12.
29. Slupska MM, Baikalov C, Luther WM, Chiang JH, Wei YF, Miller JH. Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage. J Bacteriol 1996; 178:3885-92.
30. Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, et al. Inherited variants of MYH associated with somatic G:C-.T:A mutations in colorectal tumors. Nat Genet 2002; 30:227-32.
31. Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, et al. Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-.T:A mutations. Hum Mol Genet 2002; 11:2961-7.
32. Arai K, Morishita K, Shinmura K, Kohno T, Kim SR, Nohmi T, et al. Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage. Oncogene 1997; 14:2857-61.
33. Chevillard S, Radicella JP, Levalois C, Lebeau J, Poupon MF, Oudard S, et al. Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours. Oncogene 1998; 16:3083-6.
34. Shinmura K, Yokota J. The OGG1 gene encodes a repair enzyme for oxidatively damaged DNA and is involved in human carcinogenesis. Antioxid Redox Signal 2001; 3:597-609.
35. Peng B, Hurt EM, Hodge DR, Thomas SB, Farrar WL. DNA hypermethylation and partial gene silencing of human thymine-DNA glycosylase in multiple myeloma cell lines. Epigenetics 2006; 1:138-45.
36. Robertson KA, Bullock HA, Xu Y, Tritt R, Zimmerman E, Ulbright TM, et al. Altered expression of Ape1/ref-1 in germ cell tumors and overexpression in NT2 cells confers resistance to bleomycin and radiation. Cancer Res 2001; 61:2220-5.
37. Silber JR, Bobola MS, Blank A, Schoeler KD, Haroldson PD, Huynh MB, et al. The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin Cancer Res 2002; 8:3008-18.
38. Albertella MR, Lau A, OConnor MJ. The overexpression of specialized DNA polymerases in cancer. DNA Repair (Amst) 2005; 4:583-93.
39. Srivastava DK, Husain I, Arteaga CL, Wilson SH. DNA polymerase beta expression differences in selected human tumors and cell lines. Carcinogenesis 1999; 20:1049-54.
40. Canitrot Y, Cazaux C, Frechet M, Bouayadi K, Lesca C, Salles B, et al. Overexpression of DNA polymerase beta in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs. Proc Natl Acad Sci U S A 1998; 95:12586-90.
41. Wallace SS, Murphy DL, Sweasy JB. Base excision repair and cancer. Cancer Lett 2012; 327:73-89.
42. Starcevic D, Dalal S, Sweasy JB. Is there a link between DNA polymerase beta and cancer? Cell Cycle 2004; 3:998-1001.
43. Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL. Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human. Genomics 199; 25:220-5.
44. Wu X, Wilson TE, Lieber MR. A role for FEN-1 in nonhomologous DNA end joining: the order of strand annealing and nucleolytic processing events. Proc Natl Acad Sci U S A 1999; 96:1303-8.
45. Kikuchi K, Taniguchi Y, Hatanaka A, Sonoda E, Hochegger H, Adachi N, et al. Fen-1 facilitates homologous recombination by removing divergent sequences at DNA break ends. Mol Cell Biol 2005; 25:6948-55.
46. Singh P, Zheng L, Chavez V, Qiu J, Shen B. Concerted action of exonuclease and Gap-dependent endonuclease activities of FEN-1 contributes to the resolution of triplet repeat sequences (CTG)nand (GAA)n-derived secondary structures formed during maturation of Okazaki fragments. J Biol Chem 2007; 282:3465-77.
47. Nikolova T, Christmann M, Kaina B. FEN1 is overexpressed in testis, lung and brain tumors. Anticancer Res 2009; 29:2453-9.
48. Lam JS, Seligson DB, Yu H, Li A, Eeva M, Pantuck AJ, et al. Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score. BJU Int 2006; 98:445-51.
49. LaTulippe E, Satagopan J, Smith A, Scher H, Scardino P, Reuter V, et al. Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res 2002; 62:4499-506.
50. Krause A, Combaret V, Iacono I, Lacroix B, Compagnon C, Bergeron C, et al. Genome-wide analysis of gene expression in neuroblastomas detected by mass screening. Cancer Lett 2005; 225:111-20.
51. Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, et al. Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays. Am J Pathol 2003; 162:1151-62.
52. Singh P, Yang M, Dai H, Yu D, Huang Q, Tan W, et al. Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers. Mol Cancer Res 2008; 6:1710-7.
53. Nitta M, Kozono D, Kennedy R, Stommel J, Ng K, Zinn PO, et al. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy. PLoS One 2010; 5(5):e10767.
54. Sugasawa K. Regulation of damage recognition in mammalian global genomic nucleotide excision repair. Mutat Res 2010; 685:29-37.
55. Kamileri I, Karakasilioti I, Garinis GA. Nucleotide excision repair: new tricks with old bricks Trends Genet 2012; 28:566-73.
56. Zeng-Rong N, Paterson J, Alpert L, Tsao MS, Viallet J, Alaoui-Jamali MA. Elevated DNA repair capacity is associated with intrinsic resistance of lung cancer to chemotherapy. Cancer Res 1995; 55:4760-4.
57. Wei Q, Cheng L, Xie K, Bucana CD, Dong Z. Direct correlation between DNA repair capacity and metastatic potential of K-1735 murine melanoma cells. J Invest Dermatol 1997; 108:3-6.
58. Köberle B, Masters JR, Hartley JA, Wood RD. Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours. Curr Biol 1999; 9:273-6.
59. Yang J, Xu Z, Li J, Zhang R, Zhang G, Ji H, et al. XPC epigenetic silence coupled with p53 alteration has a significant impact on bladder cancer outcome. J Urol 2010; 184:336-43.
60. Chen HY, Shao CJ, Chen FR, Kwan AL, Chen ZP. Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in human gliomas. Int J Cancer 2010; 126:1944-54.
61. Kiyohara C, Yoshimasu K. Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-Analysis. Int J Med Sci 2007; 4:59-71.
62. Martin SA, Lord CJ, Ashworth A. Therapeutic targeting of the DNA mismatch repair pathway. Clin Cancer Res 2010; 16:5107-13.
63. Pineda M, González S, Lázaro C, Blanco I, Capellá G. Detection of genetic alterations in hereditary colorectal cancer screening. Mutat Res 2010; 693:19-31.
64. Cunningham JM, Kim CY, Christensen ER, Tester DJ, Parc Y, Burgart LJ, et al. The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet 2001; 69:780-90.
65. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, et al. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 1997; 57:808-11.
66. Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 1998; 95:6870-5.
67. Esteller M, Levine R, Baylin SB, Ellenson LH, Herman JG. MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas. Oncogene 1998; 17:2413-7.
68. Fleisher AS, Esteller M, Wang S, Tamura G, Suzuki H, Yin J, et al. Hypermethylation of the hMLH1 gene promoter in human gastric cancers with microsatellite instability. Cancer Res 1999; 59:1090-5.
69. Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, et al. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Mol Cell 1998; 2:317-28.
70. Welcsh PL, King MC. BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum Mol Genet 2001; 10:705-13.
71. Li D, Kumaraswamy E, Harlan-Williams LM, Jensen RA. The role of BRCA1 and BRCA2 in prostate cancer. Front Biosci 2013; 18:1445-59.
72. Iqbal J, Ragone A, Lubinski J, Lynch HT, Moller P, Ghadirian P, et al. The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 2012; 107:2005-9.
73. Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 2000; 92:564-9.
74. Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell 2010; 40:179-204.
75. Varon R, Reis A, Henze G, von Einsiedel HG, Sperling K, Seeger K. Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL). Cancer Res 2001; 61:3570-2.
76. Cybulski C, Gó rski B, Debniak T, Gliniewicz B, Mierzejewski M, Masojc B, et al. NBS1 is a prostate cancer susceptibility gene. Cancer Res 2004; 64:1215-9.
77. Kim NG, Choi YR, Baek MJ, Kim YH, Kang H, Kim NK, et al. Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability. Cancer Res 2001; 61:36-8.
78. Kennedy RD, DAndrea AD. DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes J Clin Oncol 2006; 24:3799-808.
79. Wilson CR, Davidson SE, Margison GP, Jackson SP, Hendry JH, West CM. Expression of Ku70 correlates with survival in carcinoma of the cervix. Br J Cancer 2000; 83:1702-6.
80. Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Tsuno N, et al. The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer 2002; 95:1199-205.
81. Rigas B, Borgo S, Elhosseiny A, Balatsos V, Manika Z, Shinya H, et al. Decreased expression of DNA-dependent protein kinase, a DNA repair protein, during human colon carcinogenesis. Cancer Res 2001; 61:8381-4.
82. Yang J, Chen Z, Liu Y, Hickey RJ, Malkas LH. Altered DNA polymerase iota expression in breast cancer cells leads to a reduction in DNA replication fidelity and a higher rate of mutagenesis. Cancer Res 2004; 64:5597-607.
83. O-Wang J, Kawamura K, Tada Y, Ohmori H, Kimura H, Sakiyama S, et al. DNA polymerase kappa, implicated in spontaneous and DNA damage-induced mutagenesis, is overexpressed in lung cancer. Cancer Res 2001; 61:5366-9.
84. Boudsocq F, Benaim P, Canitrot Y, Knibiehler M, Ausseil F, Capp JP, et al. Modulation of cellular response to cisplatin by a novel inhibitor of DNA polymerase beta. Mol Pharmacol 2005; 67:1485-92.
85. Falck J, Coates J, Jackson SP. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 2005; 434:605-11.
86. Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 2005; 123:1213-26.
87. Bekker-Jensen S, Mailand N. Assembly and function of DNA double-strand break repair foci in mammalian cells. DNA Repair (Amst) 2010; 9:1219-28.
88. Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003; 300:1542-8.
89. Delacroix S, Wagner JM, Kobayashi M, Yamamoto K, Karnitz LM. The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev 2007; 21:1472-7.
90. Cotta-Ramusino C, McDonald ER 3rd, Hurov K, Sowa ME, Harper JW, Elledge SJ. A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science 2011; 332:1313-7.
91. Smits VA, Reaper PM, Jackson SP. Rapid PIKK-dependent release of CHK1 from chromatin promotes the DNA-damage checkpoint response. Curr Biol 2006; 16:150-9.
92. Mailand N, Falck J, Lukas C, Syljuasen RG, Welcker M, Bartek J, et al. Rapid destruction of human CDC25A in response to DNA damage. Science 2000; 288:1425-9.
93. Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge SJ, et al. SCFbeta-TRCP links CHK1 signaling to degradation of the CDC25A protein phosphatase. Genes Dev 2003; 17:3062-74.
94. Melixetian M, Klein DK, Srensen CS, Helin K. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. Nat Cell Biol 2009; 11:1247-53.
95. Jiang H, Reinhardt HC, Bartkova J, Tommiska J, Blomqvist C, Nevanlinna H, et al. The combined status of ATM and p53 link tumor development with therapeutic response. Genes Dev 2009; 23:1895-909.
96. Agami R, Bernards R. Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage. Cell 2000; 102:55-66.
97. Takahashi-Yanaga F, Sasaguri T. GSK-3beta regulates cyclin D1 expression: a new target for chemotherapy. Cell Signal 2008; 20:581-9.
98. Santra MK, Wajapeyee N, Green MR. F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature 2009; 459:722-5.
99. Takai H, Tominaga K, Motoyama N, Minamishima YA, Nagahama H, Tsukiyama T, et al. Aberrant cell cycle checkpoint function and early embryonic death in CHK1(-/-) mice. Genes Dev 2000; 14:1439-47.
100. Syljuasen RG, Srensen CS, Hansen LT, Fugger K, Lundin C, Johansson F, et al. Inhibition of human CHK1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol Cell Biol 2005; 25:3553-62.
101. Maya-Mendoza A, Petermann E, Gillespie DA, Caldecott KW, Jackson DA. CHK1 regulates the density of active replication origins during the vertebrate S phase. EMBO J 2007; 26:2719-31.
102. Krämer A, Mailand N, Lukas C, Syljuasen RG, Wilkinson CJ, Nigg EA, et al. Centrosome-Associated CHK1 prevents premature activation of cyclin-B-Cdk1 kinase. Nat Cell Biol 2004; 6:884-91.
103. Zachos G, Black EJ, Walker M, Scott MT, Vagnarelli P, Earnshaw WC, et al. CHK1 is required for spindle checkpoint function. Dev Cell 2007; 12:247-60.
104. Peddibhotla S, Lam MH, Gonzalez-Rimbau M, Rosen JM. The DNA-damage effector checkpoint kinase 1 is essential for chromosome segregation and cytokinesis. Proc Natl Acad Sci U S A 2009; 106:5159-64.
105. Iliakis G, Wang Y, Guan J, Wang H. DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogene 2003; 22:5834-47.
106. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, et al. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998; 282:1497-501.
107. Imbriano C, Gurtner A, Cocchiarella F, Di Agostino S, Basile V, Gostissa M, et al. Direct p53 transcriptional repression: in vivo analysis of CCAAT-containing G2/M promoters. Mol Cell Biol 2005; 25:3737-51.
108. Dalvai M, Mondesert O, Bourdon JC, Ducommun B, Dozier C. CDC25B is negatively regulated by p53 through Sp1 and NF-Y transcription factors. Oncogene 2011; 30:2282-8.
109. McKenzie L, King S, Marcar L, Nicol S, Dias SS, Schumm K, et al. p53-dependent repression of polo-like kinase-1 (PLK1). Cell Cycle 2010; 9:4200-12.
110. Bartkova J, Horejs? Z, Koed K, Krämer A, Tort F, Zieger K, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005; 434:864-70.
111. Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005; 434:907-13.
112. Gollin SM. Mechanisms leading to chromosomal instability. Semin Cancer Biol 2005; 15:33-42.
113. Eyfjord JE, Bodvarsdottir SK. Genomic instability and cancer: networks involved in response to DNA damage. Mutat Res 2005; 592:18-28.
114. Mills KD, Ferguson DO, Alt FW. The role of DNA breaks in genomic instability and tumorigenesis. Immunol Rev 2003; 194:77-95.
115. Bartek J, Bartkova J, Lukas J. DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene 2007; 26:7773-9.
116. Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature 2001; 411:366-74.
117. Barlow C, Eckhaus MA, Schäffer AA, Wynshaw-Boris A. Atm haploinsufficiency results in increased sensitivity to sublethal doses of ionizing radiation in mice. Nat Genet 1999; 21:359-60.
118. Fang Y, Tsao CC, Goodman BK, Furumai R, Tirado CA, Abraham RT, et al. ATR functions as a gene dosage-dependent tumor suppressor on a mismatch repair-deficient background. EMBO J 2004; 23:3164-74.
119. Celeste A, Difilippantonio S, Difilippantonio MJ, Fernandez-Capetillo O, Pilch DR, Sedelnikova OA, et al. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 2003; 114:371-83.
120. Bassing CH, Suh H, Ferguson DO, Chua KF, Manis J, Eckersdorff M, et al. Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 2003; 114:359-70.
121. Lam MH, Liu Q, Elledge SJ, Rosen JM. CHK1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell 2004; 6:45-59.
122. Difilippantonio S, Celeste A, Fernandez-Capetillo O, Chen HT, Reina San Martin B, Van-Laethem F, et al. Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models. Nat Cell Biol 2005; 7:675-85.
123. Zhang Y, Lim CU, Williams ES, Zhou J, Zhang Q, Fox MH, et al. NBS1 knockdown by small interfering RNA increases ionizing radiation mutagenesis and telomere association in human cells. Cancer Res 2005; 65:5544-53.
124. Balajee AS, Geard CR. Replication protein A and gamma-H2AX foci assembly is triggered by cellular response to DNA doublestrand breaks. Exp Cell Res 2004; 300:320-34.
125. Wang Y, Putnam CD, Kane MF, Zhang W, Edelmann L, Russell R, et al. Mutation in Rpa1 results in defective DNA double-strand break repair, chromosomal instability and cancer in mice. Nat Genet 2005; 37:750-5.
126. Budzowska M, Jaspers I, Essers J, de Waard H, van Drunen E, Hanada K, et al. Mutation of the mouse Rad17 gene leads to embryonic lethality and reveals a role in DNA damage-dependent recombination. EMBO J 2004; 23:3548-58.
127. Shen SX, Weaver Z, Xu X, Li C, Weinstein M, Chen L, et al. A targeted disruption of the murine Brca1 gene causes gammairradiation hypersensitivity and genetic instability. Oncogene 1998; 17:3115-24.
128. Tutt A, Ashworth A. The relationship between the roles of BRCA genes in DNA repair and cancer predisposition. Trends Mol Med 2002; 8:571-6.
129. Smilenov LB, Lieberman HB, Mitchell SA, Baker RA, Hopkins KM, Hall EJ. Combined haploinsufficiency for ATM and RAD9 as a factor in cell transformation, apoptosis, and DNA lesion repair dynamics. Cancer Res 2005; 65:933-8.
130. Balmus G, Zhu M, Mukherjee S, Lyndaker AM, Hume KR, Lee J, Riccio ML, Reeves AP, et al. Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1. Hum Mol Genet 2012; 21:3408-20.
131. Wang H, Wang H, Powell SN, Iliakis G, Wang Y. ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining. Cancer Res 2004; 64:7139-43.
132. Srensen CS, Hansen LT, Dziegielewski J, Syljuasen RG, Lundin C, Bartek J, et al. The cell-cycle checkpoint kinase CHK1 is required for mammalian homologous recombination repair. Nat Cell Biol 2005; 7:195-201.
133. Hu B, Wang H, Wang X, Lu HR, Huang C, Powell SN, et al. hit and CHK1 have opposing effects on homologous recombination repair. Cancer Res 2005; 65:8613-6.
134. Srensen CS, Syljuasen RG, Falck J, Schroeder T, Rönnstrand L, Khanna KK, et al. CHK1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiationinduced accelerated proteolysis of CDC25A. Cancer Cell 2003; 3:247-58.
135. Cliby WA, Roberts CJ, Cimprich KA, Stringer CM, Lamb JR, Schreiber SL, et al. Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints. EMBO J 1998; 17:159-69.
136. Petermann E, Maya-Mendoza A, Zachos G, Gillespie DA, Jackson DA, Caldecott KW. CHK1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Mol Cell Biol 2006; 26:3319-26.
137. Petermann E, Woodcock M, Helleday T. CHK1 promotes replication fork progression by controlling replication initiation. Proc Natl Acad Sci U S A 2010; 107:16090-5.
138. Feijoo C, Hall-Jackson C, Wu R, Jenkins D, Leitch J, Gilbert DM, et al. Activation of mammalian CHK1 during DNA replication arrest: a role for CHK1 in the intra-S phase checkpoint monitoring replication origin firing. J Cell Biol 2001; 154:913-23.
139. Paulsen RD, Cimprich KA. The ATR pathway: fine-tuning the fork. DNA Repair (Amst) 2007; 6:953-66.
140. Zhang P, Wang J, Gao W, Yuan BZ, Rogers J, Reed E. CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer. Mol Cancer 2004; 3:14.
141. Bertoni F, Codegoni AM, Furlan D, Tibiletti MG, Capella C, Broggini M. CHK1 frameshift mutations in genetically unstable colorectal and endometrial cancers. Genes Chromosomes Cancer 1999; 26:176-80.
142. Lewis KA, Mullany S, Thomas B, Chien J, Loewen R, Shridhar V, et al. Heterozygous ATR mutations in mismatch repairdeficient cancer cells have functional significance. Cancer Res 2005; 65:7091-5.
143. Menoyo A, Alazzouzi H, Esp?n E, Armengol M, Yamamoto H, Schwartz S Jr. Somatic mutations in the DNA damage-response genes ATR and CHK1 in sporadic stomach tumors with microsatellite instability. Cancer Res 2001; 61:7727-30.
144. Fishler T, Li YY, Wang RH, Kim HS, Sengupta K, Vassilopoulos A, et al. Genetic instability and mammary tumor formation in mice carrying mammary-specific disruption of CHK1 and p53. Oncogene 2010; 29:4007-17.
145. van Vugt MA, Medema RH. Getting in and out of mitosis with Polo-like kinase-1. Oncogene 2005; 24:2844-59.
146. Katayama H, Sen S. Aurora kinase inhibitors as anticancer molecules. Biochim Biophys Acta 2010; 1799:829-39.
147. Canavese M, Santo L, Raje N. Cyclin dependent kinases in cancer: potential for therapeutic intervention. Cancer Biol Ther 2012; 13:451-7.
148. Galaktionov K, Lee AK, Eckstein J, Draetta G, Meckler J, Loda M, et al. CDC25 phosphatases as potential human oncogenes. Science 1995; 269:1575-7.
149. Backert S, Gelos M, Kobalz U, Hanski ML, Böhm C, Mann B, et al. Differential gene expression in colon carcinoma cells and tissues detected with a cDNA array. Int J Cancer 1999; 82:868-74.
150. Yoshida T, Tanaka S, Mogi A, Shitara Y, Kuwano H. The clinical significance of Cyclin B1 and Wee1 expression in nonsmall-cell lung cancer. Ann Oncol 2004; 15:252-6.
151. Hwang HC, Clurman BE. Cyclin E in normal and neoplastic cell cycles. Oncogene 2005; 24:2776-86.
152. Spruck CH, Won KA, Reed SI. Deregulated cyclin E induces chromosome instability. Nature 1999; 401:297-300.
153. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell 2011; 147:275-92.
154. Mathews LA, Cabarcas SM, Farrar WL. DNA repair: the culprit for tumor-initiating cell survival? Cancer Metastasis Rev 2011; 30:185-97.
155. Winnepenninckx V, Lazar V, Michiels S, Dessen P, Stas M, Alonso SR, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 2006; 98:472-82.
156. Kauffmann A, Rosselli F, Lazar V, Winnepenninckx V, Mansuet-Lupo A, Dessen P, et al. High expression of DNA repair pathways is associated with metastasis in melanoma patients. Oncogene 2008; 27:565-73.
157. Sarasin A, Kauffmann A. Overexpression of DNA repair genes is associated with metastasis: a new hypothesis. Mutat Res 2008; 659:49-55.
158. Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 2003; 9:568-74.
159. Niida H, Nakanishi M. DNA damage checkpoints in mammals. Mutagenesis 2006; 21:3-9.
160. Broustas CG, Lieberman HB. Contributions of Rad9 to tumorigenesis. J Cell Biochem 2012; 113:742-51.
161. Toueille M, El-Andaloussi N, Frouin I, Freire R, Funk D, Shevelev I, et al. The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilization efficiency: Implications for DNA repair. Nucleic Acids Res 2004; 32:3316-24.
162. Wang W, Brandt P, Bambara RA. The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1. Proc Natl Acad Sci U S A 2004; 101:16762-7.
163. Li T, Wang Z, Zhao Y, He W, An L, Liu S, et al. Checkpoint protein Rad9 plays an important role in nucleotide excision repair. DNA Repair (Amst) 2013; 12:284-92.
164. He W, Zhao Y, Zhang C, An L, Hu Z, Liu Y, et al. Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1. Nucleic Acids Res 2008; 36:6406-17.
165. Pandita RK, Sharma GG, Laszlo A, Hopkins KM, Davey S, Chakhparonian M, et al. Mammalian Rad9 plays a role in telomere stability, S-and G2-phase-specific cell survival, and homologous recombinational repair. Mol Cell Biol 2006; 26:1850-64.
166. Günes C, Rudolph KL. The role of telomeres in stem cells and cancer. Cell 2013; 152:390-3.
167. Riboni R, Casati A, Nardo T, Zaccaro E, Ferretti L, Nuzzo F, et al. Telomeric fusions in cultured human fibroblasts as a source of genomic instability. Cancer Genet Cytogenet 1997; 95:130-6.
168. Meeker AK, Argani P. Telomere shortening occurs early during breast tumorigenesis: a cause of chromosome destabilization underlying malignant transformation? J Mammary Gland Biol Neoplasia 2004; 9:285-96.
169. Stewart SA, Weinberg RA. Telomeres: cancer to human aging. Annu Rev Cell Dev Biol 2006; 22:531-57.
170. Hopkins KM, Auerbach W, Wang XY, Hande MP, Hang H, Wolgemuth DJ, et al. Deletion of mouse rad9 causes abnormal cellular responses to DNA damage, genomic instability, and embryonic lethality. Mol Cell Biol 2004; 24:7235-48.
171. Zhu A, Zhou H, Leloup C, Marino SA, Geard CR, Hei TK, Lieberman HB. Differential impact of mouse Rad9 deletion on ionizing radiation-induced bystander effects. Radiat Res 2005; 164:655-61.
172. Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, et al. Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis. Nat Cell Biol 2000; 2:1-6.
173. Ishii H, Inageta T, Mimori K, Saito T, Sasaki H, Isobe M, et al. Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis. Proc Natl Acad Sci U S A 2005; 102:9655-60.
174. Yoshida K, Komatsu K, Wang HG, Kufe D. c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage. Mol Cell Biol 2002; 22:3292-300.
175. Yoshida K, Wang HG, Miki Y, Kufe D. Protein kinase Cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9. EMBO J 2003; 22:1431-41.
176. Gressner O, Schilling T, Lorenz K, Schulze Schleithoff E, Koch A, et al. TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J 2005; 24:2458-71.
177. Yin Y, Zhu A, Jin YJ, Liu YX, Zhang X, Hopkins KM, et al. Human RAD9 checkpoint control/proapoptotic protein can activate transcription of p21. Proc Natl Acad Sci U S A 2004; 101:8864-9.
178. Wang L, Hsu CL, Ni J, Wang PH, Yeh S, Keng P, et al. Human checkpoint protein hRad9 functions as a negative coregulator to repress androgen receptor transactivation in prostate cancer cells. Mol Cell Biol 2004; 24:2202-13.
179. Zhu A, Zhang CX, Lieberman HB. Rad9 has a functional role in human prostate carcinogenesis. Cancer Res 2008; 68:1267-74.
180. Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer 2002; 2:91-100.
181. Zeng ZZ, Jia Y, Hahn NJ, Markwart SM, Rockwood KF, Livant DL. Role of focal adhesion kinase and phosphatidylinositol 30-kinase in integrin fibronectin receptor-mediated, matrix metalloproteinase-1-dependent invasion by metastatic prostate cancer cells. Cancer Res 2006; 66:8091-9.
182. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell 2007; 129:1261-74.
183. Broustas CG, Zhu A, Lieberman HB. Rad9 protein contributes to prostate tumor progression by promoting cell migration and anoikis resistance. J Biol Chem 2012; 287:41324-33.
184. Yu YP, Landsittel D, Jing L, Nelson J, Ren B, Liu L, et al. Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy. J Clin Oncol 2004; 22:2790-9.
185. Varambally S, Yu J, Laxman B, Rhodes DR, Mehra R, Tomlins SA, et al. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell 2005; 8:393-406.
186. Chandran UR, Ma C, Dhir R, Bisceglia M, Lyons-Weiler M, Liang W, et al. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process. BMC Cancer 2007; 7:64.
187. Wang X, Zou L, Lu T, Bao S, Hurov KE, Hittelman WN, et al. Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol Cell 2006; 23:331-41.
188. Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, et al. ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature 2001; 411:969-74.
189. Bric A, Miething C, Bialucha CU, Scuoppo C, Zender L, Krasnitz A, et al. Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model. Cancer Cell 2009; 16:324-35.
190. Zhao M, Begum S, Ha PK, Westra W, Califano J. Downregulation of RAD17 in head and neck cancer. Head Neck 2008; 30:35-42.
191. Zhou Z, Jing C, Zhang L, Takeo F, Kim H, Huang Y, et al. Regulation of Rad17 Protein Turnover Unveils an Impact of Rad17-APC Cascade in Breast Carcinogenesis and Treatment. J Biol Chem 2013; 288:18134-45.
192. Wang X, Wang L, Callister MD, Putnam JB, Mao L, Li L. Human Rad17 is phosphorylated upon DNA damage and also overexpressed in primary non-small cell lung cancer tissues. Cancer Res 2001; 61:7417-21.
193. Sasaki H, Chen LB, Auclair D, Moriyama S, Kaji M, Fukai I, et al. Overexpression of Hrad17 gene in non-small cell lung cancers correlated with lymph node metastasis. Lung Cancer 2001; 34:47-52.
194. Bao S, Lu T, Wang X, Zheng H, Wang LE, Wei Q, et al. Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects. Oncogene 2004; 23:5586-93.
195. Meyerkord CL, Takahashi Y, Araya R, Takada N, Weiss RS, Wang HG. Loss of Hus1 sensitizes cells to etoposide-induced apoptosis by regulating BH3-only proteins. Oncogene 2008; 27:7248-59.
196. Kinzel B, Hall J, Natt F, Weiler J, Cohen D. Downregulation of Hus1 by antisense oligonucleotides enhances the sensitivity of human lung carcinoma cells to cisplatin. Cancer 2002; 94:1808-14.
197. Brandt PD, Helt CE, Keng PC, Bambara RA. The Rad9 protein enhances survival and promotes DNA repair following exposure to ionizing radiation. Biochem Biophys Res Commun 2006; 347:232-7.
198. Wang X, Hu B, Weiss RS, Wang Y. The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous endjoining. Oncogene 2006; 25:1980-3.
199. de la Torre J, Gil-Moreno A, Garc?a A, Rojo F, Xercavins J, Salido E, et al. Expression of DNA damage checkpoint protein Hus1 in epithelial ovarian tumors correlates with prognostic markers. Int J Gynecol Pathol 2008; 27:24-32.
200. Han L, Hu Z, Liu Y, Wang X, Hopkins KM, Lieberman HB, et al. Mouse Rad1 deletion enhances susceptibility for skin tumor development. Mol Cancer 2010; 9:67.
201. Durkacz BW, Omidiji O, Gray DA, Shall S. (ADP-ribose)n participates in DNA excision repair. Nature 1980; 283:593-6.
202. Krishnakumar R, Kraus WL. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell 2010; 39:8-24.
203. Goncalves A, Finetti P, Sabatier R, Gilabert M, Adelaide J, Borg JP, et al. Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-Analysis. Breast Cancer Res Treat 2011; 127:273-81.
204. Brenner JC, Ateeq B, Li Y, Yocum AK, Cao Q, Asangani IA, et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell 2011; 19:664-78.
205. Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello MA, Dean JL, et al. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov 2012; 2:1134-49.
206. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005; 310:644-8.
207. Gopalan A, Leversha MA, Satagopan JM, Zhou Q, Al-Ahmadie HA, Fine SW, et al. TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res 2009; 69:1400-6.
208. Rodr?guez MI, González-Flores A, Dantzer F, Collard J, de Herreros AG, Oliver FJ. Poly(ADP-ribose)-dependent regulation of Snail1 protein stability. Oncogene 2011; 30:4365-72.
209. Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol 2002; 3:155-166.
210. McPhee TR, McDonald PC, Oloumi A, Dedhar S. Integrin-linked kinase regulates E-cadherin expression through PARP-1. Dev Dyn 2008; 237:2737-47.
211. Stanisavljevic J, Porta-de-la-Riva M, Batlle R, de Herreros AG, Baulida J. The p65 subunit of NF-jB and PARP1 assist Snail1 in activating fibronectin transcription. J Cell Sci 2011; 124:4161-71.
212. Lönn P, van der Heide LP, Dahl M, Hellman U, Heldin CH, Moustakas A. PARP-1 attenuates Smad-mediated transcription. Mol Cell 2010; 40:521-32.
213. Moynahan ME, Chiu JW, Koller BH, Jasin M. Brca1 controls homology-directed DNA repair. Mol Cell 1999; 4(4):511-8.
214. Tutt A, Gabriel A, Bertwistle D, Connor F, Paterson H, Peacock J, et al. Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification. Curr Biol 1999; 9:1107-10.
215. Deng CX. BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res 2006; 34:1416-26.
216. Gorski JJ, Savage KI, Mulligan JM, McDade SS, Blayney JK, Ge Z, et al. Profiling of the BRCA1 transcriptome through microarray and ChIP-chip analysis. Nucleic Acids Res 2011; 39:9536-48.
217. Kinzler KW, Vogelstein B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 1997; 386:761, 763.
218. Monteiro AN. BRCA1: exploring the links to transcription. Trends Biochem Sci 2000; 25:469-74.
219. Wang Y, Yu J, Zhan Q. BRCA1 regulates caveolin-1 expression and inhibits cell invasiveness. Biochem Biophys Res Commun 2008; 370:201-6.
220. Coene ED, Gadelha C, White N, Malhas A, Thomas B, Shaw M, et al. A novel role for BRCA1 in regulating breast cancer cell spreading and motility. J Cell Biol 2011; 192:497-512
221. Zhu H, Yue J, Pan Z, Wu H, Cheng Y, Lu H, et al. Involvement of Caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining. PLoS One 2010; 5(8):e12055.
222. Moynahan ME, Pierce AJ, Jasin M. BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell 2001; 7:263-72.
223. Milner J, Ponder B, Hughes-Davies L, Seltmann M, Kouzarides T. Transcriptional activation functions in BRCA2. Nature 1997; 386:772-3.
224. Daniels MJ, Wang Y, Lee M, Venkitaraman AR. Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science 2004; 306:876-9.
225. Costanzo V. Brca2, Rad51 and Mre11: performing balancing acts on replication forks. DNA Repair (Amst) 2011; 10:1060-5.
226. Wang SC, Shao R, Pao AY, Zhang S, Hung MC, Su LK. Inhibition of cancer cell growth by BRCA2. Cancer Res 2002; 62:1311-4.
227. Moro L, Arbini AA, Marra E, Greco M. Down-regulation of BRCA2 expression by collagen type I promotes prostate cancer cell proliferation. J Biol Chem 2005; 280:22482-91.
228. Moro L, Arbini AA, Marra E, Greco M. Up-regulation of Skp2 after prostate cancer cell adhesion to basement membranes results in BRCA2 degradation and cell proliferation. J Biol Chem 2006; 281:22100-7 229. Moro L, Arbini AA, Yao JL, di SantAgnese PA, Marra E, Greco M. Loss of BRCA2 promotes prostate cancer cell invasion through up-regulation of matrix metalloproteinase-9. Cancer Sci 2008; 99:553-63.
229. Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol 2013; 31:1748-57.
230. Demuth I, Digweed M. The clinical manifestation of a defective response to DNA double-strand breaks as exemplified by Nijmegen breakage syndrome. Oncogene 2007; 26:7792-8.
231. Stracker TH, Petrini JH. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 2011; 12:90-103.
232. Karran P. DNA double strand break repair in mammalian cells. Curr Opin Genet Dev.2000; 10:144-50.
233. Petrini JH. The Mre11 complex and ATM: collaborating to navigate S phase. Curr Opin Cell Biol 2000; 12:293-6.
234. Chiang YC, Teng SC, Su YN, Hsieh FJ, Wu KJ. c-Myc directly regulates the transcription of the NBS1 gene involved in DNA double-strand break repair. J Biol Chem 2003; 278:19286-91.
235. Chen YC, Su YN, Chou PC, Chiang WC, Chang MC, et al. Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. J Biol Chem 2005; 280:32505-11.
236. DAmours D, Jackson SP. The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nat Rev Mol Cell Biol 2002; 3:317-27.
237. Yang MH, Chang SY, Chiou SH, Liu CJ, Chi CW, Chen PM, et al. Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer. Oncogene 2007; 26:1459-67.
238. Wu CY, Lin CT, Wu MZ, Wu KJ. Induction of HSPA4 and HSPA14 by NBS1 overexpression contributes to NBS1-induced in vitro metastatic and transformation activity. J Biomed Sci 2011; 18:1.
239. Wan R, Crowe DL. Haploinsufficiency of the Nijmegen breakage syndrome 1 gene increases mammary tumor latency and metastasis. Int J Oncol 2012; 41:345-52.
240. Klein HL. The consequences of Rad51 overexpression for normal and tumor cells. DNA Repair (Amst) 2008; 7:686-93.
241. Wang JY, Ho T, Trojanek J, Chintapalli J, Grabacka M, Stoklosa T, et al. Impaired homologous recombination DNA repair and enhanced sensitivity to DNA damage in prostate cancer cells exposed to anchorage-independence. Oncogene 2005; 24:3748-58.
242. Martinez-Marignac VL, Rodrigue A, Davidson D, Couillard M, Al-Moustafa AE, Abramovitz M, et al. The effect of a DNA repair gene on cellular invasiveness: XRCC3 over-expression in breast cancer cells. PLoS One 2011; 6(1):e16394.
243. Derheimer FA, Kastan MB. Multiple roles of ATM in monitoring and maintaining DNA integrity. FEBS Lett 2010; 584:3675-81.
244. Sun M, Guo X, Qian X, Wang H, Yang C, Brinkman KL, et al. Activation of the ATM-Snail pathway promotes breast cancer metastasis. J Mol Cell Biol 2012; 4:304-15.
245. Golding SE, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft XF, et al. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther 2009; 8:2894-902.
246. Sarsour EH, Kumar MG, Chaudhuri L, Kalen AL, Goswami PC. Redox control of the cell cycle in health and disease. Antioxid Redox Signal 2009; 11:2985-3011.
247. Pani G, Giannoni E, Galeotti T, Chiarugi P. Redox-based escape mechanism from death: the cancer lesson. Antioxid Redox Signal 2009; 11:2791-806.
248. Ditch S, Paull TT. The ATM protein kinase and cellular redox signaling: beyond the DNA damage response. Trends Biochem Sci 2012; 37:15-22.
249. Tsai YP, Wu KJ. Hypoxia-regulated target genes implicated in tumor metastasis. J Biomed Sci 2012; 19:102.
250. Lakin ND, Jackson SP. Regulation of p53 in response to DNA damage. Oncogene 1999; 18:7644-55.
251. Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JK, et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 1990; 50:7717-22.
252. Bookstein R, MacGrogan D, Hilsenbeck SG, Sharkey F, Allred DC. p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res 1993; 53:3369-73.
253. Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res 2000; 6:2969-72.
254. Hainaut P, Hollstein M. p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 2000; 77:81-137.
255. Hanel W, Moll UM. Links between mutant p53 and genomic instability. J Cell Biochem 2012; 113:433-9.
256. Song H, Hollstein M, Xu Y. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol 2007; 9:573-80.
257. Liu DP, Song H, Xu Y. A common gain of function of p53 cancer mutants in inducing genetic instability. Oncogene 2010; 29:949-56.
258. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005; 7:469-83.
259. Rausch T, Jones DT, Zapatka M, Stü tz AM, Zichner T, Weischenfeldt J, et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 2012; 148:59-71.
260. Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 1992; 70:923-35.
261. Li Y, Prives C. Are interactions with p63 and p73 involved in mutant p53 gain of oncogenic function? Oncogene 2007; 26:2220-5.
262. Singh K, Mogare D, Giridharagopalan RO, Gogiraju R, Pande G, Chattopadhyay S. p53 target gene SMAR1 is dysregulated in breast cancer: its role in cancer cell migration and invasion. PLoS One 2007; 2(7):e660.
263. Muller PA, Vousden KH, Norman JC. p53 and its mutants in tumor cell migration and invasion. J Cell Biol 2011; 192:209-18.
264. Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, et al. Mutant p53 drives invasion by promoting integrin recycling. Cell 2009; 139:1327-41.
265. Shibue T, Weinberg RA. Integrin beta1-focal adhesion kinase signaling directs the proliferation of metastatic cancer cells disseminated in the lungs. Proc Natl Acad Sci U S A 2009; 106:10290-5.
266. Huck L, Pontier SM, Zuo DM, Muller WJ. beta1-integrin is dispensable for the induction of ErbB2 mammary tumors but plays a critical role in the metastatic phase of tumor progression. Proc Natl Acad Sci U S A 2010; 107:15559-64.
267. Reymond N, Im JH, Garg R, Vega FM, Borda dAgua B, Riou P, et al. Cdc42 promotes transendothelial migration of cancer cells through b1 integrin. J Cell Biol 2012; 199:653-68.
268. Caswell PT, Vadrevu S, Norman JC. Integrins: masters and slaves of endocytic transport. Nat Rev Mol Cell Biol 2009; 10:843-53.
269. Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, et al. Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science 1994; 266:1376-80.
270. Hildesheim J, Bulavin DV, Anver MR, Alvord WG, Hollander MC, Vardanian L, et al. Gadd45a protects against UV irradiationinduced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53. Cancer Res 2002; 62:7305-15.
271. Yamasawa K, Nio Y, Dong M, Yamaguchi K, Itakura M. Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer. Clin Cancer Res 2002; 8:2563-9.
272. Wang W, Huper G, Guo Y, Murphy SK, Olson JA Jr, Marks JR. Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer. Oncogene 2005; 24:2705-14.
273. Ji J, Liu R, Tong T, Song Y, Jin S, Wu M, et al. Gadd45a regulates beta-catenin distribution and maintains cell-cell adhesion/contact. Oncogene 2007; 26:6396-405.
274. Shan Z, Li G, Zhan Q, Li D. Gadd45a inhibits cell migration and invasion by altering the global RNA expression. Cancer Biol Ther 2012; 13:1112-22.
275. Marino N, Nakayama J, Collins JW, Steeg PS. Insights into the biology and prevention of tumor metastasis provided by the Nm23 metastasis suppressor gene. Cancer Metastasis Rev 2012; 31:593-603.
276. Flrenes VA, Aamdal S, Myklebost O, Maelandsmo GM, Bruland OS, Fodstad O. Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res 1992; 52:6088-91.
277. Zhang Q, McCorkle JR, Novak M, Yang M, Kaetzel DM. Metastasis suppressor function of NM23-H1 requires its 30-50 exonuclease activity. Int J Cancer 2011; 128:40-50.
278. Jarrett SG, Novak M, Dabernat S, Daniel JY, Mellon I, Zhang Q, et al. Metastasis suppressor NM23-H1 promotes repair of UVinduced DNA damage and suppresses UV-induced melanomagenesis. Cancer Res 2012; 72:133-43.
279. Chaplet M, Rai R, Jackson-Bernitsas D, Li K, Lin SY. BRIT1/MCPH1: a guardian of genome and an enemy of tumors. Cell Cycle 2006; 5:2579-83.
280. van t-Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002; 415:530-6.
281. Rai R, Dai H, Multani AS, Li K, Chin K, Gray J, et al. BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. Cancer Cell 2006; 10:145-57.
282. Yi B, Tan SX, Tang CE, Huang WG, Cheng AL, Li C, et al. Inactivation of 14-3-3 sigma by promoter methylation correlates with metastasis in nasopharyngeal carcinoma. J Cell Biochem 2009; 106:858-66.
283. Wang XQ, Zhu YQ, Lui KS, Cai Q, Lu P, Poon RT. Aberrant Polo-like kinase 1-CDC25A pathway in metastatic hepatocellular carcinoma. Clin Cancer Res 2008; 14:6813-20.
284. Squatrito M, Gorrini C, Amati B. Tip60 in DNA damage response and growth control: many tricks in one HAT. Trends Cell Biol 2006; 16:433-42.
285. Sun Y, Jiang X, Chen S, Fernandes N, Price BD. A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci U S A 2005; 102:13182-7.
286. Lleonart ME, Vidal F, Gallardo D, Diaz-Fuertes M, Rojo F, Cuatrecasas M, et al. New p53 related genes in human tumors: significant downregulation in colon and lung carcinomas. Oncol Rep 2000; 16:603-8.
287. Sakuraba K, Yasuda T, Sakata M, Kitamura YH, Shirahata A, Goto T, et al. Down-regulation of Tip60 gene as a potential marker for the malignancy of colorectal cancer. Anticancer Res 2009; 29:3953-5.
288. Chen G, Cheng Y, Tang Y, Martinka M, Li G. Role of Tip60 in human melanoma cell migration, metastasis, and patient survival. J Invest Dermatol 2012; 132:2632-41.
289. Bonner WM, Redon CE, Dickey JS, Nakamura AJ, Sedelnikova OA, Solier S, et al. GammaH2AX and cancer. Nat Rev Cancer 2008; 8:957-67.
290. Economopoulou M, Langer HF, Celeste A, Orlova VV, Choi EY, Ma M, et al. Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med 2009; 15:553-8.
291. Rankin EB, Giaccia AJ, Hammond EM. Bringing H2AX into the angiogenesis family. Cancer Cell 2009; 15:459-61.
292. Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol 2013; 14:197-210.