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Base-excision repair of oxidative DNA damage

Abstract

Maintaining the chemical integrity of DNA in the face of assault by oxidizing agents is a constant challenge for living organisms. Base-excision repair has an important role in preventing mutations associated with a common product of oxidative damage to DNA, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine DNA glycosylases use an intricate series of steps to locate and excise 8-oxoguanine lesions efficiently against a high background of undamaged bases. The importance of preventing mutations associated with 8-oxoguanine is shown by a direct association between defects in the DNA glycosylase MUTYH and colorectal cancer. The properties of other guanine oxidation products and the associated DNA glycosylases that remove them are now also being revealed.

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Figure 1: Short-patch BER pathway for 8-oxoG.
Figure 2: Structures of 8-oxoG-containing base pairs and of several nucleosides of guanine oxidation products.
Figure 3: Recognition of 8-oxoG by OGG1 observed in the LRC of OGG1 with 8-oxoG·C-containing duplexes.
Figure 4: The LRCs of OGG1 and MutM with non-specific complexes (normal base pairs).
Figure 5: The 8-oxoG lesion search process.
Figure 6: Germline mutations observed in MUTYH in individuals with MUTYH-associated polyposis.

References

  1. Lindahl, T. Instability and decay of the primary structure of DNA. Nature 362, 709–715 (1993).

    ADS  CAS  PubMed  Google Scholar 

  2. Friedberg, E. C. DNA damage and repair. Nature 421, 436–440 (2003).

    ADS  PubMed  Google Scholar 

  3. Pfeifer, G. P. et al. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 21, 7435–7451 (2002).

    CAS  PubMed  Google Scholar 

  4. Friedberg, E. C. Inroads into base excision repair II. The discovery of the DNA glycosylases. DNA Repair (Amst.) 3, 1531–1536 (2004).

    CAS  Google Scholar 

  5. David, S. S. & Williams, S. D. Chemistry of glycosylases and endonucleases involved in base-excision repair. Chem. Rev. 98, 1221–1261 (1998).

    CAS  PubMed  Google Scholar 

  6. Fromme, J. C. & Verdine, G. L. Base excision repair. Adv. Protein Chem. 69, 1–41 (2004).

    CAS  PubMed  Google Scholar 

  7. Barnes, D. E. & Lindahl, T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu. Rev. Genet. 38, 445–476 (2004).

    CAS  PubMed  Google Scholar 

  8. Sung, J.-S. & Demple, B. Roles of base excision repair subpathways in correcting oxidized abasic sites in DNA. FEBS J. 273, 1620–1629 (2006).

    CAS  PubMed  Google Scholar 

  9. Klaunig, J. E. & Kamendulis, L. M. The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 44, 239–267 (2004).

    CAS  PubMed  Google Scholar 

  10. Neeley, W. L. & Essigmann, J. M. Mechanisms of formation, genotoxicity, and mutation of guanine oxidation products. Chem. Res. Toxicol. 19, 491–505 (2006).

    CAS  PubMed  Google Scholar 

  11. Burrows, C. M. & Muller, J. Oxidative nucleobase modifications leading to strand scission. Chem. Rev. 98, 1109–1152 (1998).

    CAS  PubMed  Google Scholar 

  12. Shibutani, S., Takeshita, M. & Grollman, A. P. Insertion of specific bases during DNA synthesis past the oxidation damaged base 8-oxodG. Nature 349, 431–434 (1991).

    ADS  CAS  PubMed  Google Scholar 

  13. Hsu, G. W., Ober, M., Carell, T. & Beese, L. S. Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase. Nature 431, 217–221 (2004).

    ADS  CAS  PubMed  Google Scholar 

  14. Michaels, M. L. & Miller, J. H. The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J. Bacteriol. 174, 6321–6325 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Krahn, J. M., Beard, W. A., Miller, H., Grollman, A. P. & Wilson, S. H. Structure of DNA polymerase β with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential. Structure 11, 121–127 (2003).

    CAS  PubMed  Google Scholar 

  16. Gedik, C. M. & Collins, A. Establishing the background level of base oxidation in human lymphocyte DNA: results on an interlaboratory validation study. FASEB J. 19, 82–84 (2005).

    CAS  PubMed  Google Scholar 

  17. Parikh, S. S., Putnam, C. D. & Tainer, J. A. Lessons learned from structural results on uracil-DNA glycosylase. Mutat. Res. 460, 183–199 (2000).

    CAS  PubMed  Google Scholar 

  18. Stivers, J. T. Site-specific DNA damage recognition by enzyme-induced base flipping. Prog. Nucleic Acid Res. Mol. Biol. 77, 37–65 (2004).

    CAS  PubMed  Google Scholar 

  19. Fromme, J. C., Banerjee, A. & Verdine, G. L. DNA glycosylase recognition and catalysis. Curr. Opin. Struct. Biol. 14, 43–49 (2004).

    CAS  PubMed  Google Scholar 

  20. Huffman, J. L., Sundheim, O. & Tainer, J. A. DNA base damage recognition and removal: new twists and grooves. Mutat. Res. 577, 55–76 (2005).

    CAS  PubMed  Google Scholar 

  21. Hitomi, K., Iwai, S. & Tainer, J. A. The intricate structural chemistry of base excision repair machinery: implications for DNA damage recognition, removal and repair. DNA Repair (Amst.) 6, 410–428 (2007).

    CAS  Google Scholar 

  22. Bruner, S. D., Norman, D. P. & Verdine, G. L. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403, 859–866 (2000).

    ADS  CAS  PubMed  Google Scholar 

  23. Banerjee, A., Yang, W., Karplus, M. & Verdine, G. L. Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA. Nature 434, 612–618 (2005).

    ADS  CAS  PubMed  Google Scholar 

  24. Radom, C. T., Banerjee, A. & Verdine, G. L. Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations. J. Biol. Chem. 282, 9182–9194 (2007).

    CAS  PubMed  Google Scholar 

  25. Banerjee, A. & Verdine, G. L. A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex. Proc. Natl Acad. Sci. USA 103, 15020–15025 (2006).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  26. Banerjee, A., Santos, W. L. & Verdine, G. L. Structure of a DNA glycosylase searching for DNA lesions. Science 311, 1153–1157 (2006).

    ADS  CAS  PubMed  Google Scholar 

  27. Fromme, J. C. & Verdine, G. L. DNA lesion recognition by the bacterial repair enzyme MutM. J. Biol. Chem. 278, 51543–51548 (2003).

    CAS  PubMed  Google Scholar 

  28. Blainey, P. C., van Oijen, A. M., Banerjee, A., Verdine, G. L. & Xie, X. S. A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA. Proc. Natl Acad. Sci. USA 103, 5752–5757 (2006).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jiang, Y. L. et al. Recognition of an unnatural difluorophenyl nucleotide by uracil DNA glycosylase. Biochemistry 43, 15429–15438 (2004).

    CAS  PubMed  Google Scholar 

  30. Noll, D. M., Gogos, A., Granek, J. A. & Clarke, N. D. The C-terminal domain of the adenine-DNA glycosylase MutY confers specificity of 8-oxoguanine–adenine mispairs and may have evolved from MutT, an 8-oxo-dGTPase. Biochemistry 38, 6374–6379 (1999).

    CAS  PubMed  Google Scholar 

  31. Chmiel, N. H., Golinelli, M.-P., Francis, A. W. & David, S. S. Efficient recognition of substrates and substrate analogs by the adenine glycosylase MutY requires the C-terminal domain. Nucleic Acids Res. 29, 553–564 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Fromme, J. C., Banerjee, A., Huang, S. J. & Verdine, G. L. Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase. Nature 427, 652–656 (2004).

    ADS  CAS  PubMed  Google Scholar 

  33. Wiederholdt, C. J., Delaney, M. O., Pope, M. A., David, S. S. & Greenberg, M. M. Repair of DNA containing FapydG and its C-nucleoside analogue by formamidopyrimidine DNA glycosylase and MutY. Biochemistry 42, 9755–9760 (2003).

    Google Scholar 

  34. Bernards, A. S., Miller, J. K., Bao, K. K. & Wong, I. Flipping duplex DNA inside out: a double base-flipping reaction mechanism by Escherichia coli MutY adenine glycosylase. J. Biol. Chem. 277, 20960–20964 (2002).

    CAS  PubMed  Google Scholar 

  35. Al-Tassan, N. et al. Inherited variants of MYH associated with somatic G:C to T:A mutations in colorectal tumors. Nature Genet. 30, 227–232 (2002).

    CAS  PubMed  Google Scholar 

  36. Fearnhead, N. S., Britton, M. P. & Bodmer, W. F. The ABC of APC. Hum. Mol. Genet. 10, 721–733 (2001).

    CAS  PubMed  Google Scholar 

  37. Chmiel, N. H., Livingston, A. L. & David, S. S. Insight into the functional consequences of inherited variants of the hMYH adenine glycosylase associated with colorectal cancer: complementation assays with hMYH variants and pre-steady-state kinetics of the corresponding mutated E. coli enzymes. J. Mol. Biol. 327, 431–443 (2003).

    CAS  PubMed  Google Scholar 

  38. Sampson, J. R., Jones, S., Dolwani, S. & Cheadle, J. P. MutYH (MYH) and colorectal cancer. Biochem. Soc. Trans. 33, 679–683 (2005).

    CAS  PubMed  Google Scholar 

  39. Cheadle, J. P. & Sampson, J. R. MUTYH-associated polyposis — from defect in base excision repair to clinical genetic testing. DNA Repair (Amst.) 6, 274–279 (2007).

    CAS  Google Scholar 

  40. Livingston, A. L., Kundu, S., Henderson-Pozzi, M., Anderson, D. W. & David, S. S. Insight into the roles of tyrosine 82 and glycine 253 in the Escherichia coli adenine glycosylase MutY. Biochemistry 44, 14179–14190 (2005).

    CAS  PubMed  Google Scholar 

  41. Pope, M. A., Chmiel, N. H. & David, S. S. Insight into the functional consequences of hMYH variants associated with colorectal cancer: distinct differences in the adenine glycosylase activity and the response to AP endonuclease of Y150C and G365D murine MYH. DNA Repair (Amst.) 4, 315–325 (2005).

    CAS  Google Scholar 

  42. Tominaga, Y. et al. MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain. Nucleic Acids Res. 32, 3198–3211 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Wooden, S. H., Bassett, H. M., Wood, T. G. & McCullough, A. K. Identification of critical residues required for the mutation avoidance function of human MutY (hMYH) and implications in colorectal cancer. Cancer Lett. 205, 89–95 (2004).

    CAS  PubMed  Google Scholar 

  44. Hirano, S. et al. Mutator phenotype of MutYH-null mouse embryonic stem cells. J. Biol. Chem. 278, 38121–38124 (2003).

    CAS  PubMed  Google Scholar 

  45. Lipton, L. et al. Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. Cancer Res. 63, 7595–7599 (2003).

    CAS  PubMed  Google Scholar 

  46. Xie, Y. et al. Deficiencies in mouse Myh and Ogg1 results in tumor predisposition and G to T mutations in codon 12 of the K-ras oncogene in lung tumors. Cancer Res. 64, 3096–3102 (2004).

    CAS  PubMed  Google Scholar 

  47. Russo, M. T. et al. Accumulation of the oxidative base lesion 8-hydroxyguanine in DNA of tumor-prone mice defective in both the Myh and Ogg1 DNA glycosylase. Cancer Res. 64, 4411–4414 (2004).

    CAS  PubMed  Google Scholar 

  48. Sieber, O. M. et al. Myh deficiency enhances intestinal tumorigenesis in multiple intestinal neoplasia (ApcMin/+) mice. Cancer Res. 64, 8876–8881 (2004).

    CAS  PubMed  Google Scholar 

  49. Sampson, J. R. et al. MYH polyposis: a new autosomal recessive form of familial adenomatous polyposis demanding reappraisal of genetic risk and family management. Lancet 362, 39–41 (2003).

    CAS  PubMed  Google Scholar 

  50. Chow, E., Thirlwell, C., Macrae, F. & Lipton, L. Colorectal cancer and inherited mutations in base-excision repair. Lancet Oncol. 5, 600–606 (2004).

    CAS  PubMed  Google Scholar 

  51. Lipton, L. & Tomlinson, I. The multiple colorectal adenoma phenotype and MYH, a excision repair gene. Clin. Gastroenterol. Hepatol. 2, 633–638 (2004).

    CAS  PubMed  Google Scholar 

  52. Tenesa, A. et al. Association of MutYH and colorectal cancer. Br. J. Cancer 95, 239–242 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Lipton, L. & Tomlinson, I. The genetics of FAP and FAP-like syndromes. Fam. Cancer 5, 221–226 (2006).

    CAS  PubMed  Google Scholar 

  54. Farrington, S. M. et al. Germline susceptibility to colorectal cancer due to base-excision repair gene defects. Am. J. Hum. Genet. 77, 112–119 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Fleischmann, C. et al. Comprehensive analysis of the contribution of germline MYH variation of early-onset colorectal cancer. Int. J. Cancer 109, 554–558 (2004).

    CAS  PubMed  Google Scholar 

  56. Strate, L. L. & Syngal, S. Hereditary colorectal cancer syndromes. Cancer Causes Control 16, 201–213 (2005).

    PubMed  Google Scholar 

  57. Jo, W. S. & Chung, D. C. Genetics of hereditary colorectal cancer. Semin. Oncol. 32, 11–23 (2005).

    CAS  PubMed  Google Scholar 

  58. Bodmer, W. F. Cancer genetics: colorectal cancer as a model. J. Hum. Genet. 51, 391–396 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Kinzler, K. W. & Vogelstein, B. Lessons from hereditary colorectal cancer. Cell 87, 159–170 (1996).

    CAS  PubMed  Google Scholar 

  60. Soreide, K., Janssen, E. A. M., Soiland, H., Korner, H. & Baak, J. P. Microsatellite instability in colorectal cancer. Br. J. Surg. 93, 395–406 (2006).

    CAS  PubMed  Google Scholar 

  61. Lindor, N. M. et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome. JAMA 296, 1507–1517 (2006).

    CAS  PubMed  Google Scholar 

  62. Venesio, T. et al. High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Gastroenterology 126, 1681–1685 (2004).

    CAS  PubMed  Google Scholar 

  63. Leite, J. S. et al. Is prophylactic colectomy indicated in patients with MYH-associated polyposis? Colorectal Dis. 7, 327–331 (2005).

    CAS  PubMed  Google Scholar 

  64. Bai, H. et al. Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis. Nucleic Acids Res. 33, 597–604 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Bai, H. et al. Functional characterization of human MutY homolog (hMYH) missense mutation (R231L) that is linked with hMYH-associated polyposis. Cancer Lett. 250, 74–81 (2007).

    CAS  PubMed  Google Scholar 

  66. Alhopuro, P. et al. A novel functionally deficient MYH variant in individuals with colorectal adenomatous polyposis. Hum. Mutat. 26, 393 (2005).

    PubMed  Google Scholar 

  67. Klunglund, A. et al. Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc. Natl Acad. Sci. USA 96, 13300–13305 (1999).

    ADS  Google Scholar 

  68. Osterod, M. et al. A global DNA repair mechanism involving Cockayne syndrome B (CSB) gene product can prevent the in vivo accumulation of endogenous oxidative DNA base damage. Oncogene 21, 8232–8239 (2002).

    CAS  PubMed  Google Scholar 

  69. Osterod, M. et al. Age-related and tissue-specific accumulation of oxidative DNA base damage in 7,8-dihydro-8-oxoguanine-DNA glycosylase (Ogg1) deficient mice. Carcinogenesis 22, 1459–1463 (2001).

    CAS  PubMed  Google Scholar 

  70. Sunesen, M., Stevnsner, T., Brosh, R. M., Dianov, G. L. & Bohr, V. A. Global genome repair of 8-oxoG in hamster cells requires a functional CSB gene product. Oncogene 21, 3571–3578 (2002).

    CAS  PubMed  Google Scholar 

  71. Cadet, J., Decarroz, C., Wang, S. Y. & Midden, W. R. Mechanisms and products of photosensitized degradation of nucleic acids and related model compounds. Isr. J. Chem. 1983, 420–429 (1983).

    Google Scholar 

  72. Ravanat, J. L. & Cadet, J. Reaction of singlet oxygen with 2'-deoxyguanosine and DNA. Isolation and characterization of the main oxidation products. Chem. Res. Toxicol. 8, 379–388 (1995).

    CAS  PubMed  Google Scholar 

  73. Ravanat, J. L., Berger, M., Bernard, F., Langlois, R. & Ouellet, R. Phthalocyanine and naphthalocyanine photosensitized oxidation of 2'-deoxyguanosine: distinct type I and type II products. Photochem. Photobiol. 55, 809–814 (1992).

    CAS  Google Scholar 

  74. Luo, W., Muller, J. G., Rachlin, E. M. & Burrows, C. J. Characterization of spiroiminodihydantoin as a product of one-electron oxidation of 8-oxo-7,8-dihydroguanosine. Org. Lett. 2, 613–616 (2000).

    CAS  PubMed  Google Scholar 

  75. Niles, J. C., Wishnok, J. S. & Tannenbaum, S. R. Spiroiminodihydantoin is the major product of the 8-oxo-7,8-dihydroguanosine reaction with peroxynitrite in the presence of thiols and guanosine photooxidation by methylene blue. Org. Lett. 3, 963–966 (2001).

    CAS  PubMed  Google Scholar 

  76. Adam, W. et al. Spiroiminodihydantoin is a major product in the photooxidation of 2'-deoxyguanosine by the triplet states and oxyl radicals generated from hydroxyacetophenone photolysis and dioxetane thermolysis. Org. Lett. 4, 537–540 (2002).

    CAS  PubMed  Google Scholar 

  77. Burrows, C. J. et al. Structure and potential mutagenicity of new hydantoin products from guanosine and 8-oxo-7,8-dihydroguanosine oxidation by transition metals. Environ. Health Perspect. 110, 713–717 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Luo, W., Muller, J. G., Rachlin, E. M. & Burrows, C. J. Characterization of hydantoin products from one-electron oxidation of 8-oxo-7,8-dihydroguanosine in a nucleoside model. Chem. Res. Toxicol. 14, 927–938 (2001).

    CAS  PubMed  Google Scholar 

  79. Kornyushyna, O., Berges, A. M., Muller, J. G. & Burrows, C. J. In vitro nucleotide misinsertion opposite the oxidized guanosine lesions spiroiminodihydantoin and guanidinohydantoin and DNA synthesis past the lesions using Escherichia coli DNA polymerase I (Klenow fragment). Biochemistry 41, 15304–15314 (2002).

    CAS  PubMed  Google Scholar 

  80. Kornyushyna, O. & Burrows, C. J. Effect of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin on proofreading by Escherichia coli DNA polymerase I (Klenow fragment) in different sequence contexts. Biochemistry 42, 13008–13018 (2003).

    CAS  PubMed  Google Scholar 

  81. Henderson, P. T. et al. The hydantoin lesions from oxidation of 7,8-dihydro-8-oxoguanine are potent sources of replication errors in vivo. Biochemistry 42, 9257–9262 (2003).

    CAS  PubMed  Google Scholar 

  82. Delaney, S., Neeley, W. L., Delaney, J. C. & Essigmann, J. M. The substrate specificity of MutY for hyperoxidized guanine lesions in vivo. Biochemistry, 46, 1448–1455 (2007).

    CAS  PubMed  Google Scholar 

  83. Leipold, M. D., Muller, J. G., Burrows, C. J. & David, S. S. Removal of hydantoin products of 8-oxoguanine oxidation by the Escherichia coli DNA repair enzyme, Fpg. Biochemistry 39, 14984–14992 (2000).

    CAS  PubMed  Google Scholar 

  84. Leipold, M. D., Workman, H., Muller, J. G., Burrows, C. J. & David, S. S. Recognition and removal of oxidized guanines in duplex DNA by the base excision repair enzymes hOGG1, yOGG1 and yOGG2. Biochemistry 42, 11373–11381 (2003).

    CAS  PubMed  Google Scholar 

  85. Hazra, T. K. et al. Repair of hydantoins, one electron oxidation product of 8-oxoguanine, by DNA glycosylases of Escherichia coli. Nucleic Acids Res. 29, 1967–1974 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Wallace, S. S., Bandaru, V., Kathe, S. D. & Bond, J. P. The enigma of endonuclease VIII. DNA Repair (Amst.) 2, 441–453 (2003).

    CAS  Google Scholar 

  87. Hailer, M. K., Slade, P. G., Martin, B. D. & Sugden, K. D. Nei-deficient Escherichia coli are sensitive to chromate and accumulate the oxidized guanine lesion spiroiminodihydantoin. Chem. Res. Toxicol. 18, 1378–1383 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Bandaru, V., Sunkara, S., Wallace, S. S. & Bond, J. P. A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII. DNA Repair (Amst.) 1, 517–529 (2002).

    CAS  Google Scholar 

  89. Hazra, T. K. et al. Identification and characterization of a human DNA glycosylase for repair of modified oxidatively damaged DNA. Proc. Natl Acad. Sci. USA 99, 3523–3528 (2002).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  90. Hazra, T. K. et al. Identification of a novel human DNA glycosylase for repair of cytosine-derived lesions. J. Biol. Chem. 277, 30417–30420 (2002).

    CAS  PubMed  Google Scholar 

  91. Morland, I. et al. Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA. Nucleic Acids Res. 30, 4926–4936 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Doublie, S., Bandaru, V., Bond, J. P. & Wallace, S. S. The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity. Proc. Natl Acad. Sci. USA 101, 10284–10289 (2004).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  93. Dou, H., Mitra, S. & Hazra, T. K. Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. J. Biol. Chem. 278, 49679–49684 (2003).

    CAS  PubMed  Google Scholar 

  94. Hailer, K. M., Slade, P. G., Martin, B. D., Rosenquist, T. A. & Sugden, K. D. Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the base excision repair glycosylases NEIL1 and NEIL2. DNA Repair (Amst.) 4, 41–50 (2005).

    CAS  Google Scholar 

  95. Das, A., Hazra, T. K., Boldogh, I., Mitra, S. & Bhakat, K. K. Induction of the human oxidized base-specific DNA glycosylase NEIL1 by reactive oxygen species. J. Biol. Chem. 280, 35272–35280 (2005).

    CAS  PubMed  Google Scholar 

  96. Rosenquist, T. A. et al. The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death. DNA Repair (Amst.) 2, 581–591 (2003).

    CAS  Google Scholar 

  97. Shinmura, K. et al. Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer. Carcinogenesis 25, 2311–2317 (2004).

    CAS  PubMed  Google Scholar 

  98. Vartanian, V. et al. The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. Proc. Natl Acad. Sci. USA 103, 1864–1869 (2006).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  99. Guan, Y. et al. MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily. Nature Struct. Biol. 5, 1058–1064 (1998).

    CAS  PubMed  Google Scholar 

  100. Lukianova, O. L. & David, S. S. A role for iron–sulfur clusters in DNA repair. Curr. Opin. Chem. Biol. 9, 145–151 (2005).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank members of the David laboratory for reading the manuscript. We also apologize to all scientists whose original studies and reviews were not included because of space limitations. Research in the laboratory of S.S.D. is funded by the National Institutes of Health, and V.L.O. has been supported by pre-doctoral fellowships from the National Institutes of Health.

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David, S., O'Shea, V. & Kundu, S. Base-excision repair of oxidative DNA damage. Nature 447, 941–950 (2007). https://doi.org/10.1038/nature05978

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