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DNA Damage Response Pathways in Cancer Predisposition and Metastasis

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'Essentials of Cancer Genomic, Computational Approaches and Precision Medicine

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Abstract

Genes involved in DNA damage response play pivotal functions in maintaining genome health. Upregulated DNA damage response and repair genes are responsible for initiating carcinogenesis and elevated resistance in cancerous cells to DNA-damaging therapy. Recent studies have confirmed the involvement of various genes in DNA repair which have additional functions in carcinogenesis specifically working as co-transcriptional factors. Though, defective DNA repair genes are linked with cancer initiation, they have more controversial roles in tumour progression and seem to be dependent on tumour type. The current chapter discusses the role of various DNA damage repair pathways along with their genes in cancer predisposition and metastasis.

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References

  1. Srivastava R, Mishra N, Singh UM, Srivastava R (2016) Genotoxicity: mechanisms and its impact on human diseases. Octa J Biosci 2016:4

    Google Scholar 

  2. Tian H, Gao Z, Li H, Zhang B, Wang G, Zhang Q, Pei D, Zheng J (2015) DNA damage response–a double-edged sword in cancer prevention and cancer therapy. Cancer Lett 358(1):8–16

    Article  CAS  PubMed  Google Scholar 

  3. Jeggo PA, Pearl LH, Carr AM (2016) DNA repair, genome stability and cancer: a historical perspective. Nat Rev Cancer 16(1):35

    Article  CAS  PubMed  Google Scholar 

  4. Topalian SL, Taube JM, Anders RA, Pardoll DM (2016) Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 16(5):275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schwertman P, Bekker-Jensen S, Mailand N (2016) Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers. Nat Rev 17(6):379

    Article  CAS  Google Scholar 

  6. Nakad R, Schumacher B (2016) DNA damage response and immune defense: links and mechanisms. Front Genet 7:147

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gorbunova V, Seluanov A (2016) DNA double strand break repair, aging and the chromatin connection. Mutat Res 788:2–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL, Bohr VA (2015) DNA damage, DNA repair, aging, and neurodegeneration. Cold Spring Harb Perspect Med 5(10):a025130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tubbs A, Nussenzweig A (2017) Endogenous DNA damage as a source of genomic instability in cancer. Cell 168(4):644–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Baylin SB, Jones PA (2016) Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol 8(9):a019505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nielsen FC, van Overeem Hansen T, Sørensen CS (2016) Hereditary breast and ovarian cancer: new genes in confined pathways. Nat Rev Cancer 16(9):599

    Article  CAS  PubMed  Google Scholar 

  12. Malik SS, Masood N, Asif M, Ahmed P, Shah ZU, Khan JS (2019) Expressional analysis of MLH1 and MSH2 in breast cancer. Curr Probl Cancer 43(2):97–105

    Article  PubMed  Google Scholar 

  13. Li Q, Damish AW, Frazier Z, Liu D, Reznichenko E, Kamburov A, Bell A, Zhao H, Jordan EJ, Gao SP (2019) ERCC2 helicase domain mutations confer nucleotide excision repair deficiency and drive cisplatin sensitivity in muscle-invasive bladder cancer. Clin Cancer Res 25(3):977–988

    Article  CAS  PubMed  Google Scholar 

  14. Murfuni I, Rass U (2016) Targeting homologous recombination repair in cancer. In: DNA repair in cancer therapy. Elsevier, London, pp 225–275

    Chapter  Google Scholar 

  15. O’Connor MJ (2015) Targeting the DNA damage response in cancer. Mol Cell 60(4):547–560

    Article  CAS  PubMed  Google Scholar 

  16. Goldstein M, Kastan MB (2015) The DNA damage response: implications for tumor responses to radiation and chemotherapy. Annu Rev Med 66:129–143

    Article  CAS  PubMed  Google Scholar 

  17. Kelley MR, Logsdon D, Fishel ML (2014) Targeting DNA repair pathways for cancer treatment: what’s new? Future Oncol 10(7):1215–1237

    Article  CAS  PubMed  Google Scholar 

  18. Jdey W, Thierry S, Russo C, Devun F, Al Abo M, Noguiez-Hellin P, Sun J-S, Barillot E, Zinovyev A, Kuperstein I (2017) Drug-driven synthetic lethality: bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors. Clin Cancer Res 23(4):1001–1011

    Article  CAS  PubMed  Google Scholar 

  19. Gorgoulis VG, Pefani DE, Pateras IS, Trougakos IP (2018) Integrating the DNA damage and protein stress responses during cancer development and treatment. J Pathol 246(1):12–40

    Article  PubMed  PubMed Central  Google Scholar 

  20. Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert PF (2015) Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect 124(6):713–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Roos WP, Thomas AD, Kaina B (2016) DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer 16(1):20

    Article  CAS  PubMed  Google Scholar 

  22. Tiwari V, Wilson DM (2019) DNA damage and associated DNA repair defects in disease and premature aging. Am J Hum Genet 105(2):237–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Llinas-Arias P, Esteller M (2017) Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update. Open Biol 7(9):170152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Knijnenburg TA, Wang L, Zimmermann MT, Chambwe N, Gao GF, Cherniack AD, Fan H, Shen H, Way GP, Greene CS (2018) Genomic and molecular landscape of DNA damage repair deficiency across The Cancer Genome Atlas. Cell Rep 23(1):239–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gao D, Herman JG, Guo M (2016) The clinical value of aberrant epigenetic changes of DNA damage repair genes in human cancer. Oncotarget 7(24):37331

    PubMed  PubMed Central  Google Scholar 

  26. Bauer NC, Corbett AH, Doetsch PW (2015) The current state of eukaryotic DNA base damage and repair. Nucleic Acids Res 43(21):10083–10101

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Malaiyandi LM, Potempa LA, Marschalk N, Jungsuwadee P, Dineley KE (2018) Alkylating-agent cytotoxicity associated with O6-methylguanine. In: Apoptosis and beyond: the many ways cells die. Wiley, Hoboken, pp 427–431

    Chapter  Google Scholar 

  28. Samavarchi Tehrani S, Mahmoodzadeh Hosseini H, Yousefi T, Abolghasemi M, Qujeq D, Maniati M, Amani J (2019) The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer. J Cell Biochem 120(2):1080–1105

    Article  CAS  Google Scholar 

  29. Hiddinga BI, Pauwels P, Janssens A, van Meerbeeck JP (2017) O6-methylguanine-DNA methyltransferase (MGMT): a drugable target in lung cancer? Lung Cancer 107:91–99

    Article  PubMed  Google Scholar 

  30. Rapkins RW, Wang F, Nguyen HN, Cloughesy TF, Lai A, Ha W, Nowak AK, Hitchins MP, McDonald KL (2015) The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide. Neuro-Oncology 17(12):1589–1598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Misawa K, Mochizuki D, Imai A, Endo S, Mima M, Misawa Y, Kanazawa T, Carey TE, Mineta H (2016) Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer. Oncotarget 7(18):26087

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kuroiwa-Trzmielina J, Wang F, Rapkins RW, Ward RL, Buchanan DD, Win AK, Clendenning M, Rosty C, Southey MC, Winship IM (2016) SNP rs16906252C> T is an expression and methylation quantitative trait locus associated with an increased risk of developing MGMT-methylated colorectal cancer. Clin Cancer Res 22(24):6266–6277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Paydar P, Asadikaram G, Nejad HZ, Akbari H, Abolhassani M, Moazed V, Nematollahi MH, Ebrahimi G, Fallah H (2019) Epigenetic modulation of BRCA-1 and MGMT genes, and histones H4 and H3 are associated with breast tumors. J Cell Biochem 120(8):13726–13736

    Article  CAS  PubMed  Google Scholar 

  34. Yu D, Cao T, Han Y-D, Huang F-S (2016) Relationships between MGMT promoter methylation and gastric cancer: a meta-analysis. OncoTargets Ther 9:6049

    Article  CAS  Google Scholar 

  35. Malik SS, Mubarik S, Masood N, Khadim MT (2018) An insight into clinical outcome of XPG polymorphisms in breast cancer. Mol Biol Rep 45(6):2369–2375

    Article  CAS  PubMed  Google Scholar 

  36. Spivak G (2015) Nucleotide excision repair in humans. DNA Repair 36:13–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Broustas CG, Lieberman HB (2014) DNA damage response genes and the development of cancer metastasis. Radiat Res 181(2):111–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gavande NS, VanderVere-Carozza PS, Hinshaw HD, Jalal SI, Sears CR, Pawelczak KS, Turchi JJ (2016) DNA repair targeted therapy: the past or future of cancer treatment? Pharmacol Ther 160:65–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Dexheimer TS (2013) DNA repair pathways and mechanisms. In: Mathews LA, Cabarcas SM, Hurt EM (eds) DNA repair of cancer stem cells. Springer, Dordrecht, pp 19–32. https://doi.org/10.1007/978-94-007-4590-2_2

    Chapter  Google Scholar 

  40. Melis JP, van Steeg H, Luijten M (2013) Oxidative DNA damage and nucleotide excision repair. Antioxid Redox Signal 18(18):2409–2419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sollier J, Stork CT, García-Rubio ML, Paulsen RD, Aguilera A, Cimprich KA (2014) Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability. Mol Cell 56(6):777–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nemzow L, Lubin A, Zhang L, Gong F (2015) XPC: going where no DNA damage sensor has gone before. DNA Repair 36:19–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH (2014) Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev 15(7):465

    Article  CAS  Google Scholar 

  44. Song X, Wang S, Hong X, Li X, Zhao X, Huai C, Chen H, Gao Z, Qian J, Wang J (2017) Single nucleotide polymorphisms of nucleotide excision repair pathway are significantly associated with outcomes of platinum-based chemotherapy in lung cancer. Sci Rep 7(1):11785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mucha B, Markiewicz L, Cuchra M, Szymczak I, Przybylowska-Sygut K, Dziki A, Majsterek I, Dziki L (2017) Nucleotide excision repair capacity and XPC, XPD gene polymorphism modulate colorectal cancer risk. Clin Colorectal Cancer 17:e435–e441

    Article  PubMed  Google Scholar 

  46. Li Y-L, Wei F, Li Y-P, Zhang L-H, Bai Y-Z (2017) A case-control study on association of nucleotide excision repair polymorphisms and its interaction with environment factors with the susceptibility to non-melanoma skin cancer. Oncotarget 8(46):80994

    PubMed  PubMed Central  Google Scholar 

  47. Romanowicz H, Strapagiel D, Słomka M, Sobalska-Kwapis M, Kępka E, Siewierska-Górska A, Zadrożny M, Bieńkiewicz J, Smolarz B (2017) New single nucleotide polymorphisms (SNPs) in homologous recombination repair genes detected by microarray analysis in Polish breast cancer patients. Clin Exp Med 17(4):541–546

    Article  CAS  PubMed  Google Scholar 

  48. Bailey MH, Ding L (2018) Genomic and molecular landscape of DNA damage repair deficiency across The Cancer Genome Atlas. Cell Rep 23(1):239–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shenoy N, Dronca R, Quevedo F, Boorjian SA, Cheville J, Costello B, Kohli M, Witzig T, Pagliaro L (2017) Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors—a major reason for enhanced chemosensitivity? Chin J Cancer Res 29(4):374

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sankhwar M, Sankhwar SN, Bansal SK, Gupta G, Rajender S (2016) Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses. Sci Rep 6:27018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Awuah SG, Riddell IA, Lippard SJ (2017) Repair shielding of platinum-DNA lesions in testicular germ cell tumors by high-mobility group box protein 4 imparts cisplatin hypersensitivity. Proc Natl Acad Sci 114(5):950–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Le May N, Calmels N, Abiayad Y, Boukli L, Semer M (2018) Xeroderma pigmentosum groups C and A in Algerian patients with deregulation of both transcription and DNA repair. J Case Rep Stud 6(4):401

    Google Scholar 

  53. Jiricny J (2006) The multifaceted mismatch-repair system. Nat Rev 7(5):335

    Article  CAS  Google Scholar 

  54. Naidu MD, Mason JM, Pica RV, Fung H, Peña LA (2010) Radiation resistance in glioma cells determined by DNA damage repair activity of Ape1/Ref-1. J Radiat Res 51(4):393–404

    Article  CAS  PubMed  Google Scholar 

  55. Groothuizen FS, Sixma TK (2016) The conserved molecular machinery in DNA mismatch repair enzyme structures. DNA Repair 38:14–23

    Article  CAS  PubMed  Google Scholar 

  56. Li F, Mao G, Tong D, Huang J, Gu L, Yang W, Li G-M (2013) The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα. Cell 153(3):590–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Li G-M (2014) New insights and challenges in mismatch repair: getting over the chromatin hurdle. DNA Repair 19:48–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Reyes GX, Schmidt TT, Kolodner RD, Hombauer H (2015) New insights into the mechanism of DNA mismatch repair. Chromosoma 124(4):443–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Xie C, Sheng H, Zhang N, Li S, Wei X, Zheng X (2016) Association of MSH6 mutation with glioma susceptibility, drug resistance and progression. Mol Clin Oncol 5(2):236–240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zauber P, Marotta S, Sabbath-Solitare M (2017) Molecular genetic changes in benign colorectal tumors synchronous with microsatellite unstable carcinomas do not support a field defect. Int J Mol Epidemiol Genet 8(3):27

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Zarandi A, Irani S, Savabkar S, Chaleshi V, Ghavideldarestani M, Mirfakhraie R, Khodadoostan M, Nazemalhosseini-Mojarad E, Aghdaei HA (2017) Evaluation of promoter methylation status of MLH1 gene in Iranian patients with colorectal tumors and adenoma polyps. Gastroenterol Hepatol Bed Bench 10(Suppl 1):S117

    PubMed  PubMed Central  Google Scholar 

  62. Tarancón-Diez M, Büttner R, Friedrichs N (2019) Enhanced tumoral MLH1-expression in MLH1-/PMS2-deficient colon cancer is indicative of sporadic colon cancer and not HNPCC. Pathol Oncol Res. https://doi.org/10.1007/s12253-018-00571-3

  63. Ma Y, Chen Y, Petersen I (2017) Expression and promoter DNA methylation of MLH1 in colorectal cancer and lung cancer. Pathol Res Pract 213(4):333–338

    Article  CAS  PubMed  Google Scholar 

  64. Fan Y, Wang Y, Fu S, Yang L, Lin S, Fan Q, Wen Q (2018) The diagnostic role of DNA methylation in sporadic endometrial cancer: a systematic review and meta-analysis. Oncotarget 9(9):8642

    Article  PubMed  Google Scholar 

  65. Hu G, Qin L, Zhang X, Ye G, Huang T (2018) Epigenetic silencing of the MLH1 promoter in relation to the development of gastric cancer and its use as a biomarker for patients with microsatellite instability: a systematic analysis. Cell Physiol Biochem 45(1):148–162

    Article  CAS  PubMed  Google Scholar 

  66. Jaiswal A, Williamson E, Patel B, Srinivasan G, Kong K, Lomelino C, Narayan S, Hromas R (2019) Splicing component ISY1 interacts with APE1 and regulates base excision repair. AACR, Philadelphia

    Google Scholar 

  67. Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC, Bohr VA (2008) Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 30(1):2–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Norjmaa B, Tulgaa K, Saitoh T (2016) Base excision repair pathway and polymorphisms of xrcc1 gene. J Mol Pathol Epidemiol 1(1):1–4

    Google Scholar 

  69. Seibold P, Behrens S, Schmezer P, Helmbold I, Barnett G, Coles C, Yarnold J, Talbot CJ, Imai T, Azria D (2015) XRCC1 polymorphism associated with late toxicity after radiation therapy in breast cancer patients. Int J Radiat Oncol 92(5):1084–1092

    Article  CAS  Google Scholar 

  70. AlMutairi F, Ali Khan Pathan A, Alanazi M, Shalaby M, Alabdulkarim HA, Alamri A, Al Naeem A, Elrobh M, Shaik JP, Khan W (2015) Association of DNA repair gene APE1 Asp148Glu polymorphism with breast cancer risk. Dis Markers 2015:869512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Du Y, He Y, Mei Z, Qian L, Shi J, Jie Z (2016) Association between genetic polymorphisms in XPD and XRCC1 genes and risks of non-small cell lung cancer in East Chinese Han population. Clin Respir J 10(3):311–317

    Article  CAS  PubMed  Google Scholar 

  72. Han B, Guo Z, Ma Y, Kang S, Wang Y, Wei Q, Wu X (2015) Association of GSTP1 and XRCC1 gene polymorphisms with clinical outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy. Int J Clin Exp Pathol 8(4):4113

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Dylawerska A, Barczak W, Wegner A, Golusinski W, Suchorska WM (2017) Association of DNA repair genes polymorphisms and mutations with increased risk of head and neck cancer: a review. Med Oncol 34(12):197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Huang S-F, Chien H-T, Liao C-T, Wang H-M, Wang Y-H (2019) Roles of XRCC1 genetic polymorphism in head and neck cancer patients receiving radiation therapy in Taiwan. AACR, Philadelphia

    Google Scholar 

  75. Feki-Tounsi M, Khlifi R, Louati I, Fourati M, Mhiri M-N, Hamza-Chaffai A, Rebai A (2017) Polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes, CYP1A1 xenobiotic metabolism gene, and tobacco are associated with bladder cancer susceptibility in Tunisian population. Environ Sci Pollut Res 24(28):22476–22484

    Article  CAS  Google Scholar 

  76. Zhong J-H, Zhao Z, Liu J, Yu H-L, Zhou J-Y, Shi R (2016) Association between APE1 Asp148Glu polymorphism and the risk of urinary cancers: a meta-analysis of 18 case–control studies. OncoTargets Ther 9:1499

    CAS  Google Scholar 

  77. Jin E-H, Kim J, Lee S-I, Hong JH (2015) Association between polymorphisms in APE1 and XRCC1 and the risk of gastric cancer in Korean population. Int J Clin Exp Med 8(7):11484

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Huang HI, Chen CH, Wang SH, Wang LH, Lin YC (2019) Effects of APE1 Asp148Glu polymorphisms on OPMD malignant transformation, and on susceptibility to and overall survival of oral cancer in Taiwan. Head Neck 41(6):1557–1564

    Article  PubMed  Google Scholar 

  79. Das S, Nath S, Bhowmik A, Ghosh SK, Choudhury Y (2016) Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis. Springerplus 5(1):227

    Article  PubMed  PubMed Central  Google Scholar 

  80. Zhou P-T, Li B, Ji J, Wang M-M, Gao C-F (2015) A systematic review and meta-analysis of the association between OGG1 Ser326Cys polymorphism and cancers. Med Oncol 32(2):31

    Article  CAS  Google Scholar 

  81. Lai C-Y, Hsieh L-L, Tang R, Santella RM, Chang-Chieh CR, Yeh C-C (2016) Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan. World J Gastroenterol 22(12):3372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Nielsen M, Hes F, Nagengast F, Weiss M, Mathus-Vliegen E, Morreau H, Breuning M, Wijnen J, Tops C, Vasen H (2007) Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. Clin Genet 71(5):427–433

    Article  CAS  PubMed  Google Scholar 

  83. Tanskanen T (2018) Genetic predisposition to colorectal cancer in young patients and in the general population

    Google Scholar 

  84. Shinmura K, Yokota J (2001) The OGG1 gene encodes a repair enzyme for oxidatively damaged DNA and is involved in human carcinogenesis. Antioxid Redox Signal 3(4):597–609

    Article  CAS  PubMed  Google Scholar 

  85. Cadet J, Davies KJ (2017) Oxidative DNA damage & repair: an introduction. Free Radic Biol Med 107:2–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Peng B, Hurt EM, Hodge DR, Thomas SB, Farrar WL (2006) DNA hypermethylation and partial gene silencing of human thymine-DNA glycosylase in multiple myeloma cell lines. Epigenetics 1(3):138–145

    Article  PubMed  Google Scholar 

  87. Maher RL, Wallace SS, Pederson DS (2019) The lyase activity of bifunctional DNA glycosylases and the 3′-diesterase activity of APE1 contribute to the repair of oxidized bases in nucleosomes. Nucleic Acids Res 47(6):2922–2931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ferreira J, Ramos AA, Almeida T, Azqueta A, Rocha E (2018) Drug resistance in glioblastoma and cytotoxicity of seaweed compounds, alone and in combination with anticancer drugs: a mini review. Phytomedicine 48:84–93

    Article  CAS  PubMed  Google Scholar 

  89. Poletto M, Lirussi L, Antoniali G, Tell G (2017) The abasic endonuclease APE1: much more than a DNA repair enzyme. In: The base excision repair pathway: molecular mechanisms and role in disease development and therapeutic design. World Scientific, Singapore, pp 219–251

    Chapter  Google Scholar 

  90. Malfatti MC, Gerratana L, Dalla E, Isola M, Damante G, Di Loreto C, Puglisi F, Tell G (2019) APE1 and NPM1 protect cancer cells from platinum compounds cytotoxicity and their expression pattern has a prognostic value in TNBC. J Exp Clin Cancer Res 38(1):309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Starcevic D, Dalal S, Sweasy JB (2004) Is there a link between DNA polymerase beta and cancer? Cell Cycle 3(8):996–999

    Article  Google Scholar 

  92. Sobol RW (2012) Genome instability caused by a germline mutation in the human DNA repair gene POLB. PLoS Genet 8(11):e1003086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Koturbash I, Baker M, Loree J, Kutanzi K, Hudson D, Pogribny I, Sedelnikova O, Bonner W, Kovalchuk O (2006) Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo. Int J Radiat Oncol 66(2):327–330

    Article  CAS  Google Scholar 

  94. Mladenov E, Magin S, Soni A (2016) Iliakis G DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: cell cycle and proliferation-dependent regulation. In: Seminars in cancer biology. Elsevier, Amsterdam, pp 51–64

    Google Scholar 

  95. Sullivan MR, Prakash R, Mihalevic MJ, Baird JM, Jasin M, Bernstein KA (2018) Abstract A08: a novel system determines the functional significance of ovarian tumor mutations in the homologous recombination gene RAD51C. AACR, Philadelphia

    Google Scholar 

  96. Majidinia M, Yousefi B (2017) DNA repair and damage pathways in breast cancer development and therapy. DNA Repair 54:22–29

    Article  CAS  PubMed  Google Scholar 

  97. Arts-de Jong M, de Bock GH, van Asperen CJ, Mourits MJ, de Hullu JA, Kets CM (2016) Germline BRCA1/2 mutation testing is indicated in every patient with epithelial ovarian cancer: a systematic review. Eur J Cancer 61:137–145

    Article  CAS  PubMed  Google Scholar 

  98. Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S, Bernards SS, Casadei S, Yi Q, Burger RA (2016) Inherited mutations in women with ovarian carcinoma. JAMA Oncol 2(4):482–490

    Article  PubMed  PubMed Central  Google Scholar 

  99. Lal G, Liu G, Schmocker B, Kaurah P, Ozcelik H, Narod SA, Redston M, Gallinger S (2000) Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations. Cancer Res 60(2):409–416

    CAS  PubMed  Google Scholar 

  100. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A (2015) Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33(3):244

    Article  CAS  PubMed  Google Scholar 

  101. Kerr L, Rewhorn MJ, Longmuir M, Fraser S, Walsh S, Andrew N, Leung HY (2016) A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer. BMC Cancer 16(1):529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Prakash R, Zhang Y, Feng W, Jasin M (2015) Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb Perspect Biol 7(4):a016600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ceccaldi R, Rondinelli B, D’Andrea AD (2016) Repair pathway choices and consequences at the double-strand break. Trends Cell Biol 26(1):52–64

    Article  CAS  PubMed  Google Scholar 

  104. Nowak J, Świątek-Kościelna B, Kałużna EM, Rembowska J, Dzikiewicz-Krawczyk A, Zawada M, Januszkiewicz-Lewandowska D (2017) Effect of irradiation on DNA synthesis, NBN gene expression and chromosomal stability in cells with NBN mutations. AMS 13(2):283

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Cybulski C, Gorski B, Dębniak T, Gliniewicz B, Mierzejewski M, Masojć B, Jakubowska A, Matyjasik J, Złowocka E, Sikorski A (2004) NBS1 is a prostate cancer susceptibility gene. Cancer Res 64(4):1215–1219

    Article  CAS  PubMed  Google Scholar 

  106. Kim N-G, Choi YR, Baek MJ, Kim YH, Kang H, Kim NK, Min JS, Kim H (2001) Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability. Cancer Res 61(1):36–38

    CAS  PubMed  Google Scholar 

  107. Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, Yamaguchi-Iwai Y, Shinohara A, Takeda S (1998) Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J 17(18):5497–5508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. O’Driscoll M, Cerosaletti KM, Girard P-M, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J (2001) DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell 8(6):1175–1185

    Article  PubMed  Google Scholar 

  109. Pannicke U, Hönig M, Schulze I, Rohr J, Heinz GA, Braun S, Janz I, Rump EM, Seidel MG, Matthes-Martin S (2010) The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. Hum Mutat 31(2):197–207

    Article  CAS  PubMed  Google Scholar 

  110. Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Saito S, Ishihara S, Kazama S, Tsuno N, Kitayama J (2003) Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku70 expression. J Exp Clin Cancer Res 22(2):223–228

    CAS  PubMed  Google Scholar 

  111. Ramzan Z, Nassri AB, Huerta S (2014) Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer. World J Gastrointest Oncol 6(7):194

    Article  PubMed  PubMed Central  Google Scholar 

  112. Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Tsuno N, Kazama S, Kitayama J, Suzuki N, Nagawa H (2002) The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer 95(6):1199–1205

    Article  PubMed  Google Scholar 

  113. Agboola AO, Ebili HO, Iyawe VO, Banjo AA, Salami BA, Rakha EA, Nolan CC, Ellis IO, Green AR (2017) Clinicopathological and molecular characteristics of Ku 70/80 expression in Nigerian breast cancer and its potential therapeutic implications. Pathol Res Pract 213(1):27–33

    Article  CAS  PubMed  Google Scholar 

  114. Takada Y, Someya M, Matsumoto Y, Satoh M, Nakata K, Hori M, Saito M, Hirokawa N, Tateoka K, Teramoto M (2016) Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy. Med Mol Morphol 49(4):210–216

    Article  CAS  PubMed  Google Scholar 

  115. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  CAS  PubMed  Google Scholar 

  116. Allen S (2018) Understanding mechanisms of metastasis of aggressive breast cancers via microfluidic means

    Google Scholar 

  117. Ronca R, Benkheil M, Mitola S, Struyf S, Liekens S (2017) Tumor angiogenesis revisited: regulators and clinical implications. Med Res Rev 37(6):1231–1274

    Article  PubMed  Google Scholar 

  118. Aslan C, Maralbashi S, Salari F, Kahroba H, Sigaroodi F, Kazemi T, Kharaziha P (2019) Tumor-derived exosomes: implication in angiogenesis and antiangiogenesis cancer therapy. J Cell Physiol 234(10):16885–16903

    Article  CAS  PubMed  Google Scholar 

  119. Jackson M, Marks L, May GH, Wilson JB (2018) The genetic basis of disease. Essays Biochem 62(5):643–723

    Article  PubMed  PubMed Central  Google Scholar 

  120. Gutschner T, Hämmerle M, Eißmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Groß M (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73(3):1180–1189

    Article  CAS  PubMed  Google Scholar 

  121. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153

    Article  CAS  PubMed  Google Scholar 

  122. Mallick B (2019) AGO-driven non-coding RNAs: codes to decode the therapeutics of diseases. Academic, London

    Google Scholar 

  123. Phan NN, Wang CY, Chen CF, Sun Z, Lai MD, Lin YC (2017) Voltage-gated calcium channels: novel targets for cancer therapy. Oncol Lett 14(2):2059–2074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Zakaria R, Platt-Higgins A, Rathi N, Crooks D, Brodbelt A, Chavredakis E, Lawson D, Jenkinson MD, Rudland PS (2016) Metastasis-inducing proteins are widely expressed in human brain metastases and associated with intracranial progression and radiation response. Br J Cancer 114(10):1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Mocellin S, Bertazza L, Benna C, Pilati P (2012) Circumventing melanoma chemoresistance by targeting DNA repair. Curr Med Chem 19(23):3893–3899

    Article  CAS  PubMed  Google Scholar 

  126. Dogrusöz M, Ruschel Trasel A, Cao J, Ҫolak S, van Pelt SI, Kroes WG, Teunisse AF, Alsafadi S, van Duinen SG, Luyten GP (2019) Differential expression of DNA repair genes in prognostically-favorable versus unfavorable uveal melanoma. Cancer 11(8):1104

    Article  Google Scholar 

  127. Kaplan AR, Glazer PM (2019) Impact of hypoxia on DNA repair and genome integrity. Mutagenesis. gez019, https://doi.org/10.1093/mutage/gez019

  128. Grichnik JM (2006) Genomic instability and tumor stem cells. J Investig Dermatol 126(6):1214–1216

    Article  CAS  PubMed  Google Scholar 

  129. Kauffmann A, Rosselli F, Lazar V, Winnepenninckx V, Mansuet-Lupo A, Dessen P, Van den Oord J, Spatz A, Sarasin A (2008) High expression of DNA repair pathways is associated with metastasis in melanoma patients. Oncogene 27(5):565

    Article  CAS  PubMed  Google Scholar 

  130. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9(4):239

    Article  CAS  PubMed  Google Scholar 

  131. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Robinson DR, Wu Y-M, Lonigro RJ, Vats P, Cobain E, Everett J, Cao X, Rabban E, Kumar-Sinha C, Raymond V (2017) Integrative clinical genomics of metastatic cancer. Nature 548(7667):297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Gupta GP, Massagué J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695

    Article  CAS  PubMed  Google Scholar 

  134. Bodmer W (2008) Genetic instability is not a requirement for tumor development. Cancer Res 68(10):3558–3561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Lord CJ, Ashworth A (2012) The DNA damage response and cancer therapy. Nature 481(7381):287

    Article  CAS  PubMed  Google Scholar 

  136. Chirnomas D, Taniguchi T, de la Vega M, Vaidya AP, Vasserman M, Hartman A-R, Kennedy R, Foster R, Mahoney J, Seiden MV (2006) Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway. Mol Cancer Ther 5(4):952–961

    Article  CAS  PubMed  Google Scholar 

  137. Ta HQ, Gioeli D (2014) The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer. Endocr Relat Cancer 21(5):R395–R407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Attari MMA, Ostadian C, Saei AA, Mihanfar A, Darband SG, Sadighparvar S, Kaviani M, Samadi H, Yousefi B, Majidinia M (2019) DNA damage response and repair in ovarian cancer: potential targets for therapeutic strategies. DNA Repair 80:59–84

    Article  CAS  Google Scholar 

  139. Alblihy A, Mesquita KA, Sadiq MT, Madhusudan S (2019) Development and implementation of precision therapies targeting base-excision DNA repair in BRCA1-associated tumors. Exp Rev Precis Med Drug Dev 4(1):11–25

    Article  Google Scholar 

  140. Doak SH (2018) Exposure to engineered nanomaterials: impact on DNA repair pathways. Int J Mol Sci 18:1515

    Google Scholar 

  141. Liu T, Huang J (2016) DNA end resection: facts and mechanisms. Genomics Proteomics Bioinformatics 14(3):126–130

    Article  PubMed  PubMed Central  Google Scholar 

  142. Lieberman HB, Panigrahi SK, Hopkins KM, Wang L, Broustas CG (2017) p53 and RAD9, the DNA damage response, and regulation of transcription networks. Radiat Res 187(4):424–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Mavragani I, Nikitaki Z, Souli M, Aziz A, Nowsheen S, Aziz K, Rogakou E, Georgakilas A (2017) Complex DNA damage: a route to radiation-induced genomic instability and carcinogenesis. Cancer 9(7):91

    Article  CAS  Google Scholar 

  144. Vodicka P, Musak L, Vodickova L, Vodenkova S, Catalano C, Kroupa M, Naccarati A, Polivkova Z, Vymetalkova V, Försti A (2018) Genetic variation of acquired structural chromosomal aberrations. Mutat Res 836:13–21

    Article  CAS  Google Scholar 

  145. Lazzerini-Denchi E, Sfeir A (2016) Stop pulling my strings—what telomeres taught us about the DNA damage response. Nat Rev 17(6):364

    Article  CAS  Google Scholar 

  146. Lieberman HB (2006) Rad9, an evolutionarily conserved gene with multiple functions for preserving genomic integrity. J Cell Biochem 97(4):690–697

    Article  CAS  PubMed  Google Scholar 

  147. Lieberman HB, Rai AJ, Friedman RA, Hopkins KM, Broustas CG (2018) Prostate cancer: unmet clinical needs and RAD9 as a candidate biomarker for patient management. Transl Cancer Res 7(Suppl 6):S651

    Article  CAS  PubMed  Google Scholar 

  148. Shiloh Y, Ziv Y (2013) The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev 14(4):197

    Article  CAS  Google Scholar 

  149. Economopoulou M, Langer HF, Celeste A, Orlova VV, Choi EY, Ma M, Vassilopoulos A, Callen E, Deng C, Bassing CH (2009) Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med 15(5):553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Wan R, Crowe DL (2012) Haploinsufficiency of the Nijmegen breakage syndrome 1 gene increases mammary tumor latency and metastasis. Int J Oncol 41(1):345–352

    CAS  PubMed  Google Scholar 

  151. Bozko P, Scholta T, Bui K, Toulany M, Rodemann H, Malek N (2018) Notch1-Cyclin E-p27kip1 and RAD17 form a network of proteins which control cellular proliferation and DNA damage response in cholangiocarcinoma. Z Gastroenterol 56(1):A4

    Google Scholar 

  152. Williams AB, Schumacher B (2016) p53 in the DNA-damage-repair process. Cold Spring Harb Perspect Med 6(5):a026070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Soliman S, Orlacchio A, Tessari A, Capece M, Visone R, Croce C, Palmieri D, Coppola V (2019) RANBP9 presence affects levels of Tip60 and activated p53 in lung cancer cells in response to DNA damage. AACR, Philadelphia

    Google Scholar 

  154. Brill E, Yokoyama T, Nair J, Yu M, Ahn Y-R, Lee J-M (2017) Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer. Oncotarget 8(67):111026

    Article  PubMed  PubMed Central  Google Scholar 

  155. Alsiary R, Brownhill SC, Brüning-Richardson A, Hutson R, Griffin N, Morrison EE, Bond J, Burchill SA, Bell SM (2018) Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer. Gene 672:34–44

    Article  CAS  PubMed  Google Scholar 

  156. Lim PX, Sutherland J, Noonan R, Dananberg A, Holloman W, Smogorzewska A, Jasin M (2017) Abstract A27: assessing somatic tumor-associated RAD51 mutations and screening for novel dominant-interfering RAD51 proteins. AACR, Philadelphia

    Google Scholar 

  157. Yamamoto Y, Koma H, Yagami T (2015) Localization of 14-3-3δ/ξ on the neuronal cell surface. Exp Cell Res 338(2):149–161

    Article  CAS  PubMed  Google Scholar 

  158. Takaoka M, Miki Y (2018) BRCA1 gene: function and deficiency. Int J Clin Oncol 23(1):36–44

    Article  CAS  PubMed  Google Scholar 

  159. Gabrielli B, Burgess A (2016) Cdc25 family phosphatases in cancer. In: Protein tyrosine phosphatases in cancer. Springer, New York, pp 283–306

    Chapter  Google Scholar 

  160. Nyberg KA (2003) Analysis of RAD9 functions: roles in the checkpoint response, DNA damage processing, and prevention of genomic instability. The University of Arizona

    Google Scholar 

  161. Kim YJ, Kim H-J, Kim HL, Kim HJ, Kim HS, Lee TR, Shin DW, Seo YR (2017) A protective mechanism of visible red light in normal human dermal fibroblasts: enhancement of GADD45A-Mediated DNA repair activity. J Investig Dermatol 137(2):466–474

    Article  CAS  PubMed  Google Scholar 

  162. Sheng Y, Xu M, Li C, Xiong Y, Yang Y, Kuang X, Wang D, Yang X (2018) Nm23-H1 is involved in the repair of ionizing radiation-induced DNA double-strand breaks in the A549 lung cancer cell line. BMC Cancer 18(1):710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Maga G, Hubscher U (2008) Repair and translesion DNA polymerases as anticancer drug targets. Anti Cancer Agents Med Chem 8(4):431–447

    Article  CAS  Google Scholar 

  164. Bu D, Tomlinson G, Lewis CM, Zhang C, Kildebeck E, Euhus DM (2006) An intronic polymorphism associated with increased XRCC1 expression, reduced apoptosis and familial breast cancer. Breast Cancer Res Treat 99(3):257–265

    Article  CAS  PubMed  Google Scholar 

  165. Xu P, Cai X, Zhang W, Li Y, Qiu P, Lu D, He X (2016) Flavonoids of Rosa roxburghii Tratt exhibit radioprotection and anti-apoptosis properties via the Bcl-2 (Ca 2+)/Caspase-3/PARP-1 pathway. Apoptosis 21(10):1125–1143

    Article  CAS  PubMed  Google Scholar 

  166. Hwang B-J, Shi G, Lu A-L (2014) Mammalian MutY homolog (MYH or MUTYH) protects cells from oxidative DNA damage. DNA Repair 13:10–21

    Article  CAS  PubMed  Google Scholar 

  167. Radhakrishnan R, Li Y, Xiang S, Yuan F, Yuan Z, Telles E, Fang J, Coppola D, Shibata D, Lane WS (2015) Histone deacetylase 10 regulates DNA mismatch repair and may involve the deacetylation of MutS homolog 2. J Biol Chem 290(37):22795–22804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Moeglin E, Desplancq D, Conic S, Oulad-Abdelghani M, Stoessel A, Chiper M, Vigneron M, Didier P, Tora L, Weiss E (2019) Uniform widespread nuclear phosphorylation of histone H2AX is an indicator of lethal DNA replication stress. Cancer 11(3):355

    Article  CAS  Google Scholar 

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  1. Fatima Jinnah Women University, Rawalpindi, Pakistan

    Saima Shakil Malik &  Iqra

  2. Armed Forces Institute of Pathology, Rawalpindi, Pakistan

    Saima Shakil Malik

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    Nosheen Masood

  2. Fatima Jinnah Women University, Rawalpindi, Pakistan

    Saima Shakil Malik

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Malik, S.S., Iqra (2020). DNA Damage Response Pathways in Cancer Predisposition and Metastasis. In: Masood, N., Shakil Malik, S. (eds) 'Essentials of Cancer Genomic, Computational Approaches and Precision Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-15-1067-0_7

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