1932

Abstract

Genomic DNA is susceptible to endogenous and environmental stresses that modify DNA structure and its coding potential. Correspondingly, cells have evolved intricate DNA repair systems to deter changes to their genetic material. Base excision DNA repair involves a number of enzymes and protein cofactors that hasten repair of damaged DNA bases. Recent advances have identified macromolecular complexes that assemble at the DNA lesion and mediate repair. The repair of base lesions generally requires five enzymatic activities: glycosylase, endonuclease, lyase, polymerase, and ligase. The protein cofactors and mechanisms for coordinating the sequential enzymatic steps of repair are being revealed through a range of experimental approaches. We discuss the enzymes and protein cofactors involved in eukaryotic base excision repair, emphasizing the challenge of integrating findings from multiple methodologies. The results provide an opportunity to assimilate biochemical findings with cell-based assays to uncover new insights into this deceptively complex repair pathway.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-013118-111315
2019-06-20
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/biochem/88/1/annurev-biochem-013118-111315.html?itemId=/content/journals/10.1146/annurev-biochem-013118-111315&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Sancar A. 2003. Structure and function of DNA photolyase and cryptochrome blue-light photoreceptors. Chem. Rev. 103:2203–38
    [Google Scholar]
  2. 2. 
    Sancar A. 2004. Photolyase and cryptochrome blue-light photoreceptors. Advances in Protein Chemistry W Yang 73–100 Cambridge, MA: Academic
    [Google Scholar]
  3. 3. 
    Lindahl T. 1982. DNA repair enzymes. Annu. Rev. Biochem. 51:61–87
    [Google Scholar]
  4. 4. 
    Lindahl T, Demple B, Robins P 1982. Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase. EMBO J 1:1359–63
    [Google Scholar]
  5. 5. 
    Mitra S, Pal BC, Foote RS 1982. O6-methylguanine-DNA methyltransferase in wild-type and ada mutants of Escherichia coli. J. Bacteriol 152:534–37
    [Google Scholar]
  6. 6. 
    Tano K, Shiota S, Collier J, Foote RS, Mitra S 1990. Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine. PNAS 87:686–90
    [Google Scholar]
  7. 7. 
    Antoniali G, Malfatti MC, Tell G 2017. Unveiling the non-repair face of the base excision repair pathway in RNA processing: a missing link between DNA repair and gene expression?. DNA Repair 56:65–74
    [Google Scholar]
  8. 8. 
    David SS, O'Shea VL, Kundu S 2007. Base-excision repair of oxidative DNA damage. Nature 447:941–50
    [Google Scholar]
  9. 9. 
    Drohat AC, Coey CT. 2016. Role of base excision “repair” enzymes in erasing epigenetic marks from DNA. Chem. Rev. 116:12711–29
    [Google Scholar]
  10. 10. 
    Krokan HE, Bjørås M. 2013. Base excision repair. Cold Spring Harb. Perspect. Biol. 5:a012583
    [Google Scholar]
  11. 11. 
    Robertson AB, Klungland A, Rognes T, Leiros I 2009. DNA repair in mammalian cells. Cell. Mol. Life Sci. 66:981–93
    [Google Scholar]
  12. 12. 
    Wallace SS. 2014. Base excision repair: a critical player in many games. DNA Repair 19:14–26
    [Google Scholar]
  13. 13. 
    Whitaker AM, Schaich MA, Smith MR, Flynn TS, Freudenthal BD 2017. Base excision repair of oxidative DNA damage: from mechanism to disease. Front. Biosci. Landmark Ed. 22:1493–522
    [Google Scholar]
  14. 14. 
    Chastain PD, Nakamura J, Rao S, Chu H, Ibrahim JG et al. 2010. Abasic sites preferentially form at regions undergoing DNA replication. FASEB J 24:3674–80
    [Google Scholar]
  15. 15. 
    Nakamura J, Swenberg JA. 1999. Endogenous apurinic/apyrimidinic sites in genomic DNA of mammalian tissues. Cancer Res 59:2522–26
    [Google Scholar]
  16. 16. 
    Klungland A, Rosewell I, Hollenbach S, Larsen E, Daly G et al. 1999. Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. PNAS 96:13300–5
    [Google Scholar]
  17. 17. 
    Lindahl T. 1993. Instability and decay of the primary structure of DNA. Nature 362:709–15
    [Google Scholar]
  18. 18. 
    Loeb LA. 1985. Apurinic sites as mutagenic intermediates. Cell 40:483–84
    [Google Scholar]
  19. 19. 
    Prasad R, Dianov GL, Bohr VA, Wilson SH 2000. FEN1 stimulation of DNA polymerase β mediates an excision step in mammalian long patch base excision repair. J. Biol. Chem. 275:4460–66
    [Google Scholar]
  20. 20. 
    Hou EW, Prasad R, Asagoshi K, Masaoka A, Wilson SH 2007. Comparative assessment of plasmid and oligonucleotide DNA substrates in measurement of in vitro base excision repair activity. Nucleic Acids Res 35:e112
    [Google Scholar]
  21. 21. 
    Chen X, Ballin JD, Della-Maria J, Tsai M-S, White EJ et al. 2009. Distinct kinetics of human DNA ligases I, IIIα, IIIβ, and IV reveal direct DNA sensing ability and differential physiological functions in DNA repair. DNA Repair 8:961–68
    [Google Scholar]
  22. 22. 
    Fortini P, Dogliotti E. 2007. Base damage and single-strand break repair: mechanisms and functional significance of short- and long-patch repair subpathways. DNA Repair 6:398–409
    [Google Scholar]
  23. 23. 
    Zharkov D. 2008. Base excision DNA repair. Cell. Mol. Life Sci. 65:1544–65
    [Google Scholar]
  24. 24. 
    Caldecott KW. 2008. Single-strand break repair and genetic disease. Nat. Rev. Genet. 9:619–31
    [Google Scholar]
  25. 25. 
    Wallace SS. 2013. DNA glycosylases search for and remove oxidized DNA bases. Environ. Mol. Mutagen. 54:691–704
    [Google Scholar]
  26. 26. 
    Parikh SS, Walcher G, Jones GD, Slupphaug G, Krokan HE et al. 2000. Uracil-DNA glycosylase–DNA substrate and product structures: Conformational strain promotes catalytic efficiency by coupled stereoelectronic effects. PNAS 97:5083–88
    [Google Scholar]
  27. 27. 
    Mol CD, Arvai AS, Slupphaug G, Kavli B, Alseth I et al. 1995. Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis. Cell 80:869–78
    [Google Scholar]
  28. 28. 
    Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA 1998. Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J 17:5214–26
    [Google Scholar]
  29. 29. 
    Sassa A, Beard WA, Prasad R, Wilson SH 2012. DNA sequence context effects on the glycosylase activity of human 8-oxoguanine DNA glycosylase. J. Biol. Chem. 287:36702–10
    [Google Scholar]
  30. 30. 
    Wong I, Lundquist AJ, Bernards AS, Mosbaugh DW 2002. Presteady-state analysis of a single catalytic turnover by Escherichia coli uracil-DNA glycosylase reveals a “pinch-pull-push” mechanism. J. Biol. Chem. 277:19424–32
    [Google Scholar]
  31. 31. 
    Beard WA, Batra VK, Wilson SH 2010. DNA polymerase structure-based insight on the mutagenic properties of 8-oxoguanine. Mutat. Res. 703:18–23
    [Google Scholar]
  32. 32. 
    Rodriguez Y, Howard MJ, Cuneo MJ, Prasad R, Wilson SH 2017. Unencumbered Pol β lyase activity in nucleosome core particles. Nucleic Acids Res 45:8901–15
    [Google Scholar]
  33. 33. 
    Kanazhevskaya LY, Koval VV, Vorobjev YN, Fedorova OS 2012. Conformational dynamics of abasic DNA upon interactions with AP endonuclease 1 revealed by stopped-flow fluorescence analysis. Biochemistry 51:1306–21
    [Google Scholar]
  34. 34. 
    Maher RL, Bloom LB. 2007. Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1. J. Biol. Chem. 282:30577–85
    [Google Scholar]
  35. 35. 
    Schermerhorn KM, Delaney S. 2013. Transient-state kinetics of apurinic/apyrimidinic (AP) endonuclease 1 acting on an authentic AP site and commonly used substrate analogs: the effect of diverse metal ions and base mismatches. Biochemistry 52:7669–77
    [Google Scholar]
  36. 36. 
    Freudenthal BD, Beard WA, Cuneo MJ, Dyrkheeva NS, Wilson SH 2015. Capturing snapshots of APE1 processing DNA damage. Nat. Struct. Mol. Biol. 22:924–31
    [Google Scholar]
  37. 37. 
    Wu W-J, Yang W, Tsai M-D 2017. How DNA polymerases catalyse replication and repair with contrasting fidelity. Nat. Rev. Chem. 1:0068
    [Google Scholar]
  38. 38. 
    Lovett ST. 2017. Template-switching during replication fork repair in bacteria. DNA Repair 56:118–28
    [Google Scholar]
  39. 39. 
    Beard WA, Wilson SH. 2014. Structure and mechanism of DNA polymerase β. Biochemistry 53:2768–80
    [Google Scholar]
  40. 40. 
    Prasad R, Batra VK, Yang X-P, Krahn JM, Pedersen LC et al. 2005. Structural insight into the DNA polymerase β deoxyribose phosphate lyase mechanism. DNA Repair 4:1347–57
    [Google Scholar]
  41. 41. 
    Pelletier H, Sawaya MR. 1996. Characterization of the metal ion binding helix–hairpin–helix motifs in human DNA polymerase β by X-ray structural analysis. Biochemistry 35:12778–87
    [Google Scholar]
  42. 42. 
    Liu Y, Beard WA, Shock DD, Prasad R, Hou EW, Wilson SH 2005. DNA polymerase β and flap endonuclease 1 enzymatic specificities sustain DNA synthesis for long patch base excision repair. J. Biol. Chem. 280:3665–74
    [Google Scholar]
  43. 43. 
    Prasad R, Beard WA, Wilson SH 1994. Studies of gapped DNA substrate binding by mammalian DNA polymerase β: dependence on 5′-phosphate group. J. Biol. Chem. 269:18096–101
    [Google Scholar]
  44. 44. 
    Prasad R, Beard WA, Chyan JY, Maciejewski MW, Mullen GP, Wilson SH 1998. Functional analysis of the amino-terminal 8-kDa domain of DNA polymerase β as revealed by site-directed mutagenesis: DNA binding and 5′-deoxyribose phosphate lyase activities. J. Biol. Chem. 273:11121–26
    [Google Scholar]
  45. 45. 
    Pelletier H, Sawaya MR, Wolfle W, Wilson SH, Kraut J 1996. Crystal structures of human DNA polymerase β complexed with DNA: implications for catalytic mechanism, processivity, and fidelity. Biochemistry 35:12742–61
    [Google Scholar]
  46. 46. 
    Beard WA, Shock DD, Wilson SH 2004. Influence of DNA structure on DNA polymerase β active site function: extension of mutagenic DNA intermediates. J. Biol. Chem. 279:31921–29
    [Google Scholar]
  47. 47. 
    Sobol RW, Horton JK, Kühn R, Gu H, Singhal RK et al. 1996. Requirement of mammalian DNA polymerase β in base excision repair. Nature 379:183–86
    [Google Scholar]
  48. 48. 
    Braithwaite EK, Prasad R, Shock DD, Hou EW, Beard WA, Wilson SH 2005. DNA polymerase λ mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts. J. Biol. Chem. 280:18469–75
    [Google Scholar]
  49. 49. 
    Tano K, Nakamura J, Asagoshi K, Arakawa H, Sonoda E et al. 2007. Interplay between DNA polymerases β and λ in repair of oxidation DNA damage in chicken DT40 cells. DNA Repair 6:869–75
    [Google Scholar]
  50. 50. 
    Vermeulen C, Bertocci B, Begg AC, Vens C 2007. Ionizing radiation sensitivity of DNA polymerase lambda-deficient cells. Radiat. Res. 168:683–88
    [Google Scholar]
  51. 51. 
    García-Díaz M, Domínguez O, López-Fernández LA, de Lera LT, Saníger ML et al. 2000. DNA polymerase lambda (Pol λ), a novel eukaryotic DNA polymerase with a potential role in meiosis. J. Mol. Biol. 301:851–67
    [Google Scholar]
  52. 52. 
    Moon AF, Garcia-Diaz M, Bebenek K, Davis BJ, Zhong X et al. 2007. Structural insight into the substrate specificity of DNA polymerase μ. Nat. Struct. Mol. Biol. 14:45–53
    [Google Scholar]
  53. 53. 
    Batra VK, Beard WA, Shock DD, Krahn JM, Pedersen LC, Wilson SH 2006. Magnesium induced assembly of a complete DNA polymerase catalytic complex. Structure 14:757–66
    [Google Scholar]
  54. 54. 
    Garcia-Diaz M, Bebenek K, Krahn JM, Kunkel TA, Pedersen LC 2005. A closed conformation for the Pol λ catalytic cycle. Nat. Struct. Mol. Biol. 12:97–98
    [Google Scholar]
  55. 55. 
    Loc'h J, Rosario S, Delarue M 2016. Structural basis for a new templated activity by terminal deoxynucleotidyl transferase: implications for V(D)J recombination. Structure 24:1452–63
    [Google Scholar]
  56. 56. 
    Garcia-Díaz M, Bebenek K, Kunkel TA, Blanco L 2001. Identification of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in human DNA polymerase λ: a possible role in base excision repair. J. Biol. Chem. 276:34659–63
    [Google Scholar]
  57. 57. 
    Bienstock RJ, Beard WA, Wilson SH 2014. Phylogenetic analysis and evolutionary origins of DNA polymerase X-family members. DNA Repair 22:77–88
    [Google Scholar]
  58. 58. 
    Ellenberger TA, Tomkinson AE. 2008. Eukaryotic DNA ligases: structural and functional insights. Annu. Rev. Biochem. 77:313–38
    [Google Scholar]
  59. 59. 
    Çağlayan M, Horton JK, Dai D-P, Stefanick DF, Wilson SH 2017. Oxidized nucleotide insertion by pol β confounds ligation during base excision repair. Nat. Commun. 8:14045
    [Google Scholar]
  60. 60. 
    Çağlayan M, Wilson SH. 2018. Pol μ dGTP mismatch insertion opposite T coupled with ligation reveals promutagenic DNA repair intermediate. Nat. Commun. 9:4213
    [Google Scholar]
  61. 61. 
    Prasad R, Singhal RK, Srivastava DK, Molina JT, Tomkinson AE, Wilson SH 1996. Specific interaction of DNA polymerase β and DNA ligase I in a multiprotein base excision repair complex from bovine testis. J. Biol. Chem. 271:16000–7
    [Google Scholar]
  62. 62. 
    Prasad R, Williams JG, Hou EW, Wilson SH 2012. Pol β associated complex and base excision repair factors in mouse fibroblasts. Nucleic Acids Res 40:11571–82
    [Google Scholar]
  63. 63. 
    Srivastava DK, Vande Berg BJ, Prasad R, Molina JT, Beard WA et al. 1998. Mammalian abasic site base excision repair: identification of the reaction sequence and rate-determining steps. J. Biol. Chem. 273:21203–9
    [Google Scholar]
  64. 64. 
    Caldecott KW, McKeown CK, Tucker JD, Ljungquist S, Thompson LH 1994. An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Mol. Cell. Biol. 14:68–76
    [Google Scholar]
  65. 65. 
    Lakshmipathy U, Campbell C. 1999. The human DNA ligase III gene encodes nuclear and mitochondrial proteins. Mol. Cell. Biol. 19:3869–76
    [Google Scholar]
  66. 66. 
    Gao Y, Katyal S, Lee Y, Zhao J, Rehg JE et al. 2011. DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair. Nature 471:240–44
    [Google Scholar]
  67. 67. 
    Simsek D, Furda A, Gao Y, Artus J, Brunet E et al. 2011. Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair. Nature 471:245–48
    [Google Scholar]
  68. 68. 
    Hassa PO, Hottiger MO. 2008. The diverse biological roles of mammalian PARPs, a small but powerful family of poly-ADP-ribose polymerases. Front. Biosci. 13:3046–82
    [Google Scholar]
  69. 69. 
    Schreiber V, Dantzer F, Ame J-C, de Murcia G 2006. Poly(ADP-ribose): novel functions for an old molecule. Nat. Rev. Mol. Cell Biol. 7:517–28
    [Google Scholar]
  70. 70. 
    de Murcia G, Ménissier de Murcia J 1994. Poly(ADP-ribose) polymerase: a molecular nick-sensor. Trends Biochem. Sci. 19:172–76
    [Google Scholar]
  71. 71. 
    D'Amours D, Desnoyers S, D'Silva I, Poirier GG 1999. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem. J. 342:249–68
    [Google Scholar]
  72. 72. 
    Prasad R, Horton JK, Chastain PD, Gassman NR, Freudenthal BD et al. 2014. Suicidal cross-linking of PARP-1 to AP site intermediates in cells undergoing base excision repair. Nucleic Acids Res 42:6337–51
    [Google Scholar]
  73. 73. 
    Ganguly B, Dolfi SC, Rodriguez-Rodriguez L, Ganesan S, Hirshfield KM 2016. Role of biomarkers in the development of PARP inhibitors. Biomark. Cancer 8:15–25
    [Google Scholar]
  74. 74. 
    Rouleau M, Patel A, Hendzel MJ, Kaufmann SH, Poirier GG 2010. PARP inhibition: PARP1 and beyond. Nat. Rev. Cancer 10:293–301
    [Google Scholar]
  75. 75. 
    Murai J, Marchand C, Shahane SA, Sun H, Huang R et al. 2014. Identification of novel PARP inhibitors using a cell-based TDP1 inhibitory assay in a quantitative high-throughput screening platform. DNA Repair 21:177–82
    [Google Scholar]
  76. 76. 
    Horton JK, Wilson SH. 2013. Predicting enhanced cell killing through PARP inhibition. Mol. Cancer Res. 11:13–18
    [Google Scholar]
  77. 77. 
    Horton JK, Stefanick DF, Prasad R, Gassman NR, Kedar PS, Wilson SH 2014. Base excision repair defects invoke hypersensitivity to PARP inhibition. Mol. Cancer Res. 12:1128–39
    [Google Scholar]
  78. 78. 
    Gassman NR, Wilson SH. 2015. Micro-irradiation tools to visualize base excision repair and single-strand break repair. DNA Repair 31:52–63
    [Google Scholar]
  79. 79. 
    Cuneo MJ, London RE. 2010. Oxidation state of the XRCC1 N-terminal domain regulates DNA polymerase β binding affinity. PNAS 107:6805–10
    [Google Scholar]
  80. 80. 
    Horton JK, Seddon HJ, Zhao M-L, Gassman NR, Janoshazi AK et al. 2017. Role of the oxidized form of XRCC1 in protection against extreme oxidative stress. Free Radic. Biol. Med. 107:292–300
    [Google Scholar]
  81. 81. 
    Horton JK, Stefanick DF, Gassman NR, Williams JG, Gabel SA et al. 2013. Preventing oxidation of cellular XRCC1 affects PARP-mediated DNA damage responses. DNA Repair 12:774–85
    [Google Scholar]
  82. 82. 
    Horton JK, Gassman NR, Dunigan BD, Stefanick DF, Wilson SH 2015. DNA polymerase β-dependent cell survival independent of XRCC1 expression. DNA Repair 26:23–29
    [Google Scholar]
  83. 83. 
    Prasad R, Beard WA, Strauss PR, Wilson SH 1998. Human DNA polymerase β deoxyribose phosphate lyase: substrate specificity and catalytic mechanism. J. Biol. Chem. 273:15263–70
    [Google Scholar]
  84. 84. 
    Çağlayan M, Batra VK, Sassa A, Prasad R, Wilson SH 2014. Role of polymerase β in complementing aprataxin deficiency during abasic-site base excision repair. Nat. Struct. Mol. Biol. 21:497–99
    [Google Scholar]
  85. 85. 
    Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F et al. 2001. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 104:107–17
    [Google Scholar]
  86. 86. 
    Chou K-M, Kukhanova M, Cheng Y-C 2000. A novel action of human apurinic/apyrimidinic endonuclease: excision of l-configuration deoxyribonucleoside analogs from the 3′ termini of DNA. J. Biol. Chem. 275:31009–15
    [Google Scholar]
  87. 87. 
    Whitaker AM, Flynn TS, Freudenthal BD 2018. Molecular snapshots of APE1 proofreading mismatches and removing DNA damage. Nat. Commun. 9:399
    [Google Scholar]
  88. 88. 
    Interthal H, Chen HJ, Champoux JJ 2005. Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages. J. Biol. Chem. 280:36518–28
    [Google Scholar]
  89. 89. 
    Ledesma FC, El Khamisy SF, Zuma MC, Osborn K, Caldecott KW 2009. A human 5′-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage. Nature 461:674–78
    [Google Scholar]
  90. 90. 
    Das A, Wiederhold L, Leppard JB, Kedar P, Prasad R et al. 2006. NEIL2-initiated, APE-independent repair of oxidized bases in DNA: evidence for a repair complex in human cells. DNA Repair 5:1439–48
    [Google Scholar]
  91. 91. 
    Hanssen-Bauer A, Solvang-Garten K, Sundheim O, Peña-Diaz J, Andersen S et al. 2011. XRCC1 coordinates disparate responses and multiprotein repair complexes depending on the nature and context of the DNA damage. Environ. Mol. Mutagen. 52:623–35
    [Google Scholar]
  92. 92. 
    Liu Y, Prasad R, Beard WA, Kedar PS, Hou EW et al. 2007. Coordination of steps in single-nucleotide base excision repair mediated by apurinic/apyrimidinic endonuclease 1 and DNA polymerase β. J. Biol. Chem. 282:13532–41
    [Google Scholar]
  93. 93. 
    Lan L, Nakajima S, Oohata Y, Takao M, Okano S et al. 2004. In situ analysis of repair processes for oxidative DNA damage in mammalian cells. PNAS 101:13738–43
    [Google Scholar]
  94. 94. 
    Iyama T, Wilson DM. 2016. Elements that regulate the DNA damage response of proteins defective in Cockayne syndrome. J. Mol. Biol. 428:62–78
    [Google Scholar]
  95. 95. 
    Abdou I, Poirier GG, Hendzel MJ, Weinfeld M 2015. DNA ligase III acts as a DNA strand break sensor in the cellular orchestration of DNA strand break repair. Nucleic Acids Res 43:875–92
    [Google Scholar]
  96. 96. 
    Campalans A, Kortulewski T, Amouroux R, Menoni H, Vermeulen W, Radicella JP 2013. Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair. Nucleic Acids Res 41:3115–29
    [Google Scholar]
  97. 97. 
    Horton JK, Stefanick DF, Zhao M-L, Janoshazi AK, Gassman NR et al. 2017. XRCC1-mediated repair of strand breaks independent of PNKP binding. DNA Repair 60:52–63
    [Google Scholar]
  98. 98. 
    Antoniali G, Lirussi L, Poletto M, Tell G 2013. Emerging roles of the nucleolus in regulating the DNA damage response: the noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example. Antioxid. Redox Signal. 20:621–39
    [Google Scholar]
  99. 99. 
    Bauer NC, Doetsch PW, Corbett AH 2015. Mechanisms regulating protein localization. Traffic 16:1039–61
    [Google Scholar]
  100. 100. 
    Kubota Y, Takanami T, Higashitani A, Horiuchi S 2009. Localization of X-ray cross complementing gene 1 protein in the nuclear matrix is controlled by casein kinase II-dependent phosphorylation in response to oxidative damage. DNA Repair 8:953–60
    [Google Scholar]
  101. 101. 
    Horton JK, Stefanick DF, Çağlayan M, Zhao M-L, Janoshazi AK et al. 2018. XRCC1 phosphorylation affects aprataxin recruitment and DNA deadenylation activity. DNA Repair 64:26–33
    [Google Scholar]
  102. 102. 
    Vande Berg BJ, Beard WA, Wilson SH 2001. DNA structure and aspartate 276 influence nucleotide binding to human DNA polymerase β: implication for the identity of the rate-limiting conformational change. J. Biol. Chem. 276:3408–16
    [Google Scholar]
  103. 103. 
    Prasad R, Shock DD, Beard WA, Wilson SH 2010. Substrate channeling in mammalian base excision repair pathways: passing the baton. J. Biol. Chem. 285:40479–88
    [Google Scholar]
  104. 104. 
    Wilson SH, Kunkel TA. 2000. Passing the baton in base excision repair. Nat. Struct. Biol. 7:176–78
    [Google Scholar]
  105. 105. 
    Berg OG, Winter RB, Von Hippel PH 1981. Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory. Biochemistry 20:6929–48
    [Google Scholar]
  106. 106. 
    Parker JB, Bianchet MA, Krosky DJ, Friedman JI, Amzel LM, Stivers JT 2007. Enzymatic capture of an extrahelical thymine in the search for uracil in DNA. Nature 449:433–37
    [Google Scholar]
  107. 107. 
    Schonhoft JD, Kosowicz JG, Stivers JT 2013. DNA translocation by human uracil DNA glycosylase: role of DNA phosphate charge. Biochemistry 52:2526–35
    [Google Scholar]
  108. 108. 
    Esadze A, Stivers JT. 2018. Facilitated diffusion mechanisms in DNA base excision repair and transcriptional activation. Chem. Rev. 118:11298–323
    [Google Scholar]
  109. 109. 
    Howard MJ, Wilson SH. 2018. DNA scanning by base excision repair enzymes and implications for pathway coordination. DNA Repair 71:101–7
    [Google Scholar]
  110. 110. 
    Hedglin M, Zhang Y, O'Brien PJ 2013. Isolating contributions from intersegmental transfer to DNA searching by alkyladenine DNA glycosylase. J. Biol. Chem. 288:24550–59
    [Google Scholar]
  111. 111. 
    Hedglin M, Zhang Y, O'Brien PJ 2015. Probing the DNA structural requirements for facilitated diffusion. Biochemistry 54:557–66
    [Google Scholar]
  112. 112. 
    Howard MJ, Wilson SH. 2017. Processive searching ability varies among members of the gap-filling DNA polymerase X family. J. Biol. Chem. 292:17473–81
    [Google Scholar]
  113. 113. 
    Howard MJ, Rodriguez Y, Wilson SH 2017. DNA polymerase β uses its lyase domain in a processive search for DNA damage. Nucleic Acids Res 45:3822–32
    [Google Scholar]
  114. 114. 
    Mao P, Brown AJ, Malc EP, Mieczkowski PA, Smerdon MJ et al. 2017. Genome-wide maps of alkylation damage, repair, and mutagenesis in yeast reveal mechanisms of mutational heterogeneity. Genome Res 27:1674–84
    [Google Scholar]
  115. 115. 
    Rodriguez Y, Hinz JM, Smerdon MJ 2015. Accessing DNA damage in chromatin: preparing the chromatin landscape for base excision repair. DNA Repair 32:113–19
    [Google Scholar]
  116. 116. 
    Breslin C, Hornyak P, Ridley A, Rulten SL, Hanzlikova H et al. 2015. The XRCC1 phosphate-binding pocket binds poly (ADP-ribose) and is required for XRCC1 function. Nucleic Acids Res 43:6934–44
    [Google Scholar]
  117. 117. 
    Loizou JI, El-Khamisy SF, Zlatanou A, Moore DJ, Chan DW et al. 2004. The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell 117:17–28
    [Google Scholar]
  118. 118. 
    Cairns J, Robins P, Sedgwick B, Talmud P 1981. The inducible repair of alkylated DNA. Prog. Nucleic Acid Res. Mol. Biol. 26:237–44
    [Google Scholar]
  119. 119. 
    Demple B, Harrison L. 1994. Repair of oxidative damage to DNA: enzymology and biology. Annu. Rev. Biochem. 63:915–48
    [Google Scholar]
  120. 120. 
    Lindahl T, Sedgwick B, Sekiguchi M, Nakabeppu Y 1988. Regulation and expression of the adaptive response to alkylating agents. Annu. Rev. Biochem. 57:133–57
    [Google Scholar]
  121. 121. 
    Walker GC. 1984. Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol. Rev 48:60–93
    [Google Scholar]
  122. 122. 
    Fornace AJ Jr, Zmudzka B, Hollander MC, Wilson SH. 1989. Induction of β-polymerase mRNA by DNA-damaging agents in Chinese hamster ovary cells. Mol. Cell. Biol. 9:851–53
    [Google Scholar]
  123. 123. 
    Johnston LH, White JH, Johnson AL, Lucchini G, Plevani P 1987. The yeast DNA polymerase I transcript is regulated in both the mitotic cell cycle and in meiosis and is also induced after DNA damage. Nucleic Acids Res 15:5017–30
    [Google Scholar]
  124. 124. 
    Ramana CV, Boldogh I, Izumi T, Mitra S 1998. Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals. PNAS 95:5061–66
    [Google Scholar]
  125. 125. 
    Samson L, Schwartz JL. 1980. Evidence for an adaptive DNA repair pathway in CHO and human skin fibroblast cell lines. Nature 287:861–63
    [Google Scholar]
  126. 126. 
    Hanawalt PC. 2002. Subpathways of nucleotide excision repair and their regulation. Oncogene 21:8949–56
    [Google Scholar]
  127. 127. 
    Lehmann AR. 2011. Ubiquitin-family modifications in the replication of DNA damage. FEBS Lett 585:2772–79
    [Google Scholar]
  128. 128. 
    Gassman NR, Coskun E, Jaruga P, Dizdaroglu M, Wilson SH 2016. Combined effects of high-dose bisphenol A and oxidizing agent (KBrO3) on cellular microenvironment, gene expression, and chromatin structure of Ku70-deficient mouse embryonic fibroblasts. Environ. Health Perspect. 124:1241–52
    [Google Scholar]
  129. 129. 
    Chen K-H, Yakes FM, Srivastava DK, Singhal RK, Sobol RW et al. 1998. Up-regulation of base excision repair correlates with enhanced protection against a DNA damaging agent in mouse cell lines. Nucleic Acids Res 26:2001–7
    [Google Scholar]
  130. 130. 
    Szczesny B, Mitra S. 2005. Effect of aging on intracellular distribution of abasic (AP) endonuclease 1 in the mouse liver. Mechan. Ageing Dev. 126:1071–78
    [Google Scholar]
  131. 131. 
    Boiteux S, Coste F, Castaing B 2017. Repair of 8-oxo-7,8-dihydroguanine in prokaryotic and eukaryotic cells: properties and biological roles of the Fpg and OGG1 DNA N-glycosylases. Free Radic. Biol. Med. 107:179–201
    [Google Scholar]
  132. 132. 
    Kim M, Huang T, Miller JH 2003. Competition between MutY and mismatch repair at A⋅C mispairs in vivo. J. Bacteriol. 185:4626–29
    [Google Scholar]
  133. 133. 
    Xie Y, Yang H, Cunanan C, Okamoto K, Shibata D et al. 2004. Deficiencies in mouse Myh and Ogg1 result in tumor predisposition and G to T mutations in codon 12 of the K-Ras oncogene in lung tumors. Cancer Res 64:3096–102
    [Google Scholar]
  134. 134. 
    Michaels ML, Cruz C, Grollman AP, Miller JH 1992. Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. PNAS 89:7022–25
    [Google Scholar]
  135. 135. 
    Evert BA, Salmon TB, Song B, Jingjing L, Siede W, Doetsch PW 2004. Spontaneous DNA damage in Saccharomyces cerevisiae elicits phenotypic properties similar to cancer cells. J. Biol. Chem. 279:22585–94
    [Google Scholar]
  136. 136. 
    Swanson RL, Morey NJ, Doetsch PW, Jinks-Robertson S 1999. Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathways for DNA base damage in Saccharomyces cerevisiae. Mol. Cell. Biol 19:2929–35
    [Google Scholar]
  137. 137. 
    Sampath H, Batra AK, Vartanian V, Carmical JR, Prusak D et al. 2011. Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice. Am. J. Physiol. Endocrinol. Metab. 300:E724–34
    [Google Scholar]
  138. 138. 
    Sampath H, McCullough AK, Lloyd RS 2012. Regulation of DNA glycosylases and their role in limiting disease. Free Radical Res 46:460–78
    [Google Scholar]
  139. 139. 
    Sampath H, Vartanian V, Rollins MR, Sakumi K, Nakabeppu Y, Lloyd RS 2012. 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PLOS ONE 7:e51697
    [Google Scholar]
  140. 140. 
    Vartanian V, Lowell B, Minko IG, Wood TG, Ceci JD et al. 2006. The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. PNAS 103:1864–69
    [Google Scholar]
  141. 141. 
    Vartanian V, Tumova J, Dobrzyn P, Dobrzyn A, Nakabeppu Y et al. 2017. 8-Oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle. PLOS ONE 12:e0181687
    [Google Scholar]
  142. 142. 
    Chan MK, Ocampo-Hafalla MT, Vartanian V, Jaruga P, Kirkali G et al. 2009. Targeted deletion of the genes encoding NTH1 and NEIL1 DNA N-glycosylases reveals the existence of novel carcinogenic oxidative damage to DNA. DNA Repair 8:786–94
    [Google Scholar]
  143. 143. 
    Daimon M, Oizumi T, Toriyama S, Karasawa S, Jimbu Y et al. 2009. Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM. Biochem. Biophys. Res. Commun. 386:26–29
    [Google Scholar]
  144. 144. 
    Thameem F, Puppala S, Lehman DM, Stern MP, Blangero J et al. 2010. The Ser(326)Cys polymorphism of 8-oxoguanine glycosylase 1 (OGG1) is associated with type 2 diabetes in Mexican Americans. Hum. Hered. 70:97–101
    [Google Scholar]
  145. 145. 
    Meas R, Burak MJ, Sweasy JB 2017. DNA repair and systemic lupus erythematosus. DNA Repair 56:174–82
    [Google Scholar]
  146. 146. 
    Senejani AG, Liu Y, Kidane D, Maher SE, Zeiss CJ et al. 2014. Mutation of POLB causes lupus in mice. Cell Rep 6:1–8
    [Google Scholar]
  147. 147. 
    Ray S, Breuer G, DeVeaux M, Zelterman D, Bindra R, Sweasy JB 2018. DNA polymerase beta participates in DNA end-joining. Nucleic Acids Res 46:242–55
    [Google Scholar]
  148. 148. 
    Moor NA, Lavrik OI. 2018. Protein–protein interactions in DNA base excision repair. Biochemistry (Moscow) 83:411–22
    [Google Scholar]
  149. 149. 
    Esadze A, Rodriguez G, Weiser BP, Cole PA, Stivers JT 2017. Measurement of nanoscale DNA translocation by uracil DNA glycosylase in human cells. Nucleic Acids Res 45:12413–24
    [Google Scholar]
  150. 150. 
    Perera L, Beard WA, Pedersen LG, Wilson SH 2014. Applications of quantum mechanical/molecular mechanical methods to the chemical insertion step of DNA and RNA. Advances in Protein Chemistry and Structural Biology ZC Christov 83–113 Cambridge, MA: Academic
    [Google Scholar]
  151. 151. 
    Schlick T, Arora K, Beard WA, Wilson SH 2012. Pre-chemistry conformational changes in DNA polymerase mechanisms. Theor. Chem. Acc. 131:1287
    [Google Scholar]
  152. 152. 
    Nakamura T, Zhao Y, Yamagata Y, Hua Y-J, Yang W 2012. Watching DNA polymerase η make a phosphodiester bond. Nature 487:196–201
    [Google Scholar]
  153. 153. 
    Esadze A, Rodriguez G, Cravens SL, Stivers JT 2017. AP-endonuclease 1 accelerates turnover of human 8-oxoguanine DNA glycosylase by preventing retrograde binding to the abasic-site product. Biochemistry 56:1974–86
    [Google Scholar]
  154. 154. 
    Prasad R, Çağlayan M, Dai D-P, Nadalutti CA, Zhao M-L et al. 2017. DNA polymerase β: a missing link of the base excision repair machinery in mammalian mitochondria. DNA Repair 60:77–88
    [Google Scholar]
  155. 155. 
    Sykora P, Kanno S, Akbari M, Kulikowicz T, Baptiste BA et al. 2017. DNA polymerase beta participates in mitochondrial DNA repair. Mol. Cell. Biol. 37:e00237–17
    [Google Scholar]
  156. 156. 
    Kaufman BA, Van Houten B 2017. POLB: a new role of DNA polymerase beta in mitochondrial base excision repair. DNA Repair 60:A1–5
    [Google Scholar]
  157. 157. 
    Krasich R, Copeland WC. 2017. DNA polymerases in the mitochondria: a critical review of the evidence. Front. Biosci. Landmark Ed. 22:692–709
    [Google Scholar]
  158. 158. 
    García-Gómez S, Reyes A, Martínez-Jiménez MI, Chocrón ES, Mourón S et al. 2013. PrimPol, an archaic primase/polymerase operating in human cells. Mol. Cell 52:541–53
    [Google Scholar]
  159. 159. 
    Torregrosa-Muñumer R, Forslund JME, Goffart S, Pfeiffer A, Stojkovič G et al. 2017. PrimPol is required for replication reinitiation after mtDNA damage. PNAS 114:11398–403
    [Google Scholar]
  160. 160. 
    Wisnovsky S, Jean SR, Liyanage S, Schimmer A, Kelley SO 2016. Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes. Nat. Chem. Biol. 12:567–73
    [Google Scholar]
  161. 161. 
    Wisnovsky S, Sack T, Pagliarini DJ, Laposa RR, Kelley SO 2018. DNA polymerase θ increases mutational rates in mitochondrial DNA. ACS Chem. Biol. 13:900–8
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-013118-111315
Loading
/content/journals/10.1146/annurev-biochem-013118-111315
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error