Seminars in Radiation Oncology
Volume 20, Issue 4 , Pages 241-249 , October 2010

Targeting Base Excision Repair as a Sensitization Strategy in Radiotherapy

  • Conchita Vens, PhD
  • ,
  • Adrian C. Begg, PhD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Adrian C. Begg, PhD, Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

References 

  1. Hegde ML, Hazra TK, Mitra S. Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res. 2008;18:27–47
  2. Almeida KH, Sobol RW. A unified view of base excision repair: Lesion-dependent protein complexes regulated by post-translational modification. DNA Repair (Amst). 2007;6:695–711
  3. Caldecott KW. Single-strand break repair and genetic disease. Nat Rev Genet. 2008;9:619–631
  4. An Q, Robins P, Lindahl T, et al. C –> T mutagenesis and gamma-radiation sensitivity due to deficiency in the Smug1 and Ung DNA glycosylases. EMBO J. 2005;24:2205–2213
  5. Aller P, Rould MA, Hogg M, et al. A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycol. Proc Natl Acad Sci U S A. 2007;104:814–818
  6. Sobol RW, Horton JK, Kuhn R, et al. Requirement of mammalian DNA polymerase-beta in base-excision repair. Nature. 1996;379:183–186
  7. Vermeulen C, Verwijs-Janssen M, Cramers P, et al. Role for DNA polymerase beta in response to ionizing radiation. DNA Repair (Amst). 2007;6:202–212
  8. Vermeulen C, Verwijs-Janssen M, Begg AC, et al. Cell cycle phase dependent role of DNA polymerase beta in DNA repair and survival after ionizing radiation. Radiother Oncol. 2008;86:391–398
  9. Breslin C, Caldecott KW. DNA 3'-phosphatase activity is critical for rapid global rates of single-strand break repair following oxidative stress. Mol Cell Biol. 2009;29:4653–4662
  10. Shinmura K, Tao H, Goto M, et al. Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer. Carcinogenesis. 2004;25:2311–2317
  11. Rosenquist TA, Zaika E, Fernandes AS, et al. The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death. DNA Repair (Amst). 2003;2:581–591
  12. Audebert M, Chevillard S, Levalois C, et al. Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney. Cancer Res. 2000;60:4740–4744
  13. Bristow RG. Oxygen, DNA repair and genetic instability: Implications for radiation oncology. Radiol Oncol. 2010;90:S22-S22
  14. Sak SC, Harnden P, Johnston CF, et al. APE1 and XRCC1 protein expression levels predict cancer-specific survival following radical radiotherapy in bladder cancer. Clin Cancer Res. 2005;11:6205–6211
  15. Fan R, Kumaravel TS, Jalali F, et al. Defective DNA strand break repair after DNA damage in prostate cancer cells: Implications for genetic instability and prostate cancer progression. Cancer Res. 2004;64:8526–8533
  16. Bobola MS, Blank A, Berger MS, et al. Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas. Clin Cancer Res. 2001;7:3510–3518
  17. Bobola MS, Finn LS, Ellenbogen RG, et al. Apurinic/apyrimidinic endonuclease activity is associated with response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors. Clin Cancer Res. 2005;11:7405–7414
  18. Kelley MR, Cheng L, Foster R, et al. Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref 1 in prostate cancer. Clin Cancer Res. 2001;7:824–830
  19. Zheng L, Dai H, Zhou M, et al. Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Nat Med. 2007;13:812–819
  20. Starcevic D, Dalal S, Sweasy JB. Is there a link between DNA polymerase beta and cancer?. Cell Cycle. 2004;3:998–1001
  21. Lang T, Dalal S, Chikova A, et al. The E295K DNA polymerase beta gastric cancer-associated variant interferes with base excision repair and induces cellular transformation. Mol Cell Biol. 2007;27:5587–5596
  22. Lang T, Maitra M, Starcevic D, et al. A DNA polymerase beta mutant from colon cancer cells induces mutations. Proc Natl Acad Sci U S A. 2004;101:6074–6079
  23. Sweasy JB, Lang T, Starcevic D, et al. Expression of DNA polymerase {beta} cancer-associated variants in mouse cells results in cellular transformation. Proc Natl Acad Sci U S A. 2005;102:14350–14355
  24. Albertella MR, Lau A, O'Connor MJ. The overexpression of specialized DNA polymerases in cancer. DNA Repair (Amst). 2005;4:583–593
  25. Yoshizawa K, Jelezcova E, Brown AR, et al. Gastrointestinal hyperplasia with altered expression of DNA polymerase beta. PLoS ONE. 2009;5:e6493-e2009
  26. Trivedi RN, Wang XH, Jelezcova E, et al. Human methyl purin DNA glycosylase and DNA polymerase beta expression collectively predict sensitivity to temozolomide. Mol Pharmacol. 2008;74:505–516
  27. Robertson KA, Bullock HA, Xu Y, 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;61:2220–2225
  28. Herring CJ, West CM, Wilks DP, et al. Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (APE1, APEX, ref 1) are associated with the intrinsic radiosensitivity of cervical cancers. Br J Cancer. 1998;78:1128–1133
  29. Jenner TJ, Fulford J, O'Neill P. Contribution of base lesions to radiation-induced clustered DNA damage: Implication for models of radiation response. Radiat Res. 2001;156:590–593
  30. Kozmin SG, Sedletska Y, Reynaud-Angelin A, et al. The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/incision at base damage in eukaryotic cells. Nucleic Acids Res. 2009;37:1767–1777
  31. Weinfeld M, Rasouli-Nia A, Chaudhry MA, et al. Response of base excision repair enzymes to complex DNA lesions. Radiat Res. 2001;156:584–589
  32. Yang N, Galick H, Wallace SS. Attempted base excision repair of ionizing radiation damage in human lymphoblastoid cells produces lethal and mutagenic double strand breaks. DNA Repair (Amst). 2004;3:1323–1334
  33. Clairmont CA, Sweasy JB. Dominant negative rat DNA polymerase beta mutants interfere with base excision repair in Saccharomyces cerevisiae. J Bacteriol. 1996;178:656–661
  34. Vens C, Dahmen-Mooren E, Verwijs-Janssen M, et al. The role of DNA polymerase beta in determining sensitivity to ionizing radiation in human tumor cells. Nucleic Acids Res. 2002;30:2995–3004
  35. Vens C, Hofland I, Begg AC. Involvement of DNA polymerase beta in repair of ionizing radiation damage as measured by in vitro plasmid assays. Radiat Res. 2007;168:281–291
  36. Neijenhuis S, Verwijs-Janssen M, Kasten-Pisula U, et al. Mechanism of cell killing after ionizing radiation by a dominant negative DNA polymerase beta. DNA Repair (Amst). 2009;8:336–346
  37. Raaphorst GP, Cybulski SE, Sobol R, et al. The response of human breast tumour cell lines with altered polymerase beta levels to cisplatin and radiation. Anticancer Res. 2001;21:2079–2083
  38. Makridakis NM, Caldas Ferraz LF, Reichardt JK. Genomic analysis of cancer tissue reveals that somatic mutations commonly occur in a specific motif. Hum Mutat. 2009;30:39–48
  39. Ide H, Kotera M. Human DNA glycosylases involved in the repair of oxidatively damaged DNA. Biol Pharm Bull. 2004;27:480–485
  40. Bernstein NK, Karimi-Busheri F, Rasouli-Nia A, et al. Polynucleotide kinase as a potential target for enhancing cytotoxicity by ionizing radiation and topoisomerase I inhibitors. Anti Cancer Agents Med Chem. 2008;8:358–367
  41. Freschauf GK, Karimi-Busheri F, Ulaczyk-Lesanko A, et al. Identification of a small molecule inhibitor of the human DNA repair enzyme polynucleotide kinase/phosphatase. Cancer Res. 2009;69:7739–7746
  42. Fishel ML, Kelley MR. The DNA base excision repair protein Ape1/ref 1 as a therapeutic and chemopreventive target. Mol Aspects Med. 2007;28:375–395
  43. Batuello CN, Kelley MR, Dynlacht JR. Role of Ape1 and base excision repair in the radioresponse and heat-radiosensitization of HeLa cells. Anticancer Res. 2009;29:1319–1325
  44. Xiang DB, Chen ZT, Wang D, et al. Chimeric adenoviral vector ad 5/F35-mediated APE1 siRNA enhances sensitivity of human colorectal cancer cells to radiotherapy in vitro and in vivo. Cancer Gene Ther. 2008;15:625–635
  45. Simeonov A, Kulkarni A, Dorjsuren D, et al. Identification and characterization of inhibitors of human apurinic/apyrimidinic endonuclease APE1. PLoS ONE. 2009;4:e5740-e2009
  46. Mizushina Y, Kasai N, Miura K, et al. Structural relationship of lithocholic acid derivatives binding to the N-terminal 8-kDa domain of DNA polymerase beta. Biochemistry. 2004;43:10669–10677
  47. Hazan C, Boudsocq F, Gervais V, et al. Structural insights on the pamoic acid and the 8-kDa domain of DNA polymerase beta complex: Towards the design of higher-affinity inhibitors. BMC Struct Biol. 2008;8:22
  48. Yang J, Parsons J, Nicolay NH, et al. Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy. Oncogene. 2009;29:463–468
  49. Neijenhuis S, Begg AC, Vens C. Radiosensitization by a dominant negative to DNA polymerase beta is DNA polymerase beta-independent and XRCC1-dependent. Radiother Oncol. 2005;76:123–128
  50. Mitchell JB, Russo A, Cook JA, et al. Radiobiology and clinical application of halogenated pyrimidine radiosensitizers. Int J Radiat Biol. 1989;56:827–836
  51. Schulz CA, Mehta MP, Badie B, et al. Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: A phase I clinical study. Int J Radiat Oncol Biol Phys. 2004;59:1107–1115
  52. Berry SE, Kinsella TJ. Targeting DNA mismatch repair for radiosensitization. Semin Radiat Oncol. 2001;11:300–315
  53. Taverna P, Liu L, Hwang HS, et al. Methoxyamine potentiates DNA single strand breaks and double strand breaks induced by temozolomide in colon cancer cells. Mutat Res. 2001;485:269–281
  54. Yan T, Seo Y, Schupp JE, et al. Methoxyamine potentiates iododeoxyuridine-induced radiosensitization by altering cell cycle kinetics and enhancing senescence. Mol Cancer Ther. 2006;5:893–902
  55. Golding SE, Rosenberg E, Neill S, et al. Extracellular signal-related kinase positively regulates ataxia telangiectasia mutated, homologous recombination repair, and the DNA damage response. Cancer Res. 2007;67:1046–1053
  56. Wang H, Wang X, Iliakis G, et al. Caffeine could not efficiently sensitize homologous recombination repair-deficient cells to ionizing radiation-induced killing. Radiat Res. 2003;159:420–425
  57. Miyagawa K. Clinical relevance of the homologous recombination machinery in cancer therapy. Cancer Sci. 2008;99:187–194
  58. Tanner B, Grimme S, Schiffer I, et al. Nuclear expression of apurinic/apyrimidinic endonuclease increases with progression of ovarian carcinomas. Gynecol Oncol. 2004;92:568–577
  59. Zhang Y, Wang J, Xiang D, et al. Alterations in the expression of the apurinic/apyrimidinic endonuclease-one/redox factor 1 (APE1/ref 1) in human ovarian cancer and identification of the therapeutic potential of APE1/ref 1 inhibitor. Int J Oncol. 2009;35:1069–1079
  60. Yang N, Chaudhry MA, Wallace SS. Base excision repair by hNTH1 and hOGG1: A two edged sword in the processing of DNA damage in gamma-irradiated human cells. DNA Repair (Amst). 2006;5:43–51
  61. Kohno T, Shinmura K, Tosaka M, et al. Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene. 1998;16:3219–3225
  62. Srivastava DK, Husain I, Arteaga CL, et al. DNA polymerase beta expression differences in selected human tumors and cell lines. Carcinogenesis. 1999;20:1049–1054
  63. Miura M, Watanabe H, Okochi K, et al. Biological response to ionizing radiation in mouse embryo fibroblasts with a targeted disruption of the DNA polymerase beta gene. Radiat Res. 2000;153:773–780
  64. Dobashi Y, Shuin T, Tsuruga H, et al. DNA polymerase beta gene mutation in human prostate cancer. Cancer Res. 1994;54:2827–2829
  65. Dong Z, Zhao G, Zhao Q, et al. [A study of DNA polymerase beta mutation in human esophageal cancer]. Zhonghua Yi Xue Za Zhi. 2002;82:899–902
  66. Dong ZM, Zheng NG, Wu JL, et al. Difference in expression level and localization of DNA polymerase beta among human esophageal cancer focus, adjacent and corresponding normal tissues. Dis Esophagus. 2006;19:172–176
  67. Tan XH, Zhao M, Pan KF, et al. Frequent mutation related with overexpression of DNA polymerase beta in primary tumors and precancerous lesions of human stomach. Cancer Lett. 2005;220:101–114
  68. Zhao GQ, Wang T, Zhao Q, et al. Mutation of DNA polymerase beta in esophageal carcinoma of different regions. World J Gastroenterol. 2005;11:4618–4622
  69. Thompson TE, Rogan PK, Risinger JI, et al. Splice variants but not mutations of DNA polymerase beta are common in bladder cancer. Cancer Res. 2002;62:3251–3256
  70. vanAnkeren SC, Murray D, Stafford PM, et al. Cell survival and recovery processes in Chinese hamster AA8 cells and in two radiosensitive clones. Radiat Res. 1988;115:223–237

PII: S1053-4296(10)00039-1

doi: 10.1016/j.semradonc.2010.05.005

Seminars in Radiation Oncology
Volume 20, Issue 4 , Pages 241-249 , October 2010