Abstract
In living cells, the DNA molecule is subject to attack from reactive oxygen species generated as the result of endogenous oxidative metabolism and exogenous factors, such as ionising radiation. Reactive oxygen species can produce a variety of DNA lesions, including DNA single strand breaks containing modified 3′-ends that are a threat to cellular genomic integrity. However, the cell is equipped with multiple repair mechanisms that are able to efficiently remove the lesion followed by subsequent repair of the DNA strand break. The majority of small base damages in DNA are repaired by proteins of the base excision repair pathway that involves removal of the damaged base by a DNA glycosylase, incision of the AP site produced by AP endonuclease and gap filling and ligation by DNA polymerase β and DNA ligase IIIα-XRCC1 complex, respectively. However, the repair of DNA single strand breaks containing 3′-end modifications may require a different subset of enzymes due to the different complexity of the damage. In this review, we summarise the proteins currently identified as playing a major role in the repair of DNA single strand breaks containing 3′-end lesions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Dianov GL, O’Neill P, Goodhead DT. Securing genome stability by orchestrating DNA repair: Removal of radiation-induced clustered lesions in DNA. BioEssays 2001; 23:745–749.
Henner WD, Rodriguez LO, Hecht SM et al. γ Ray induced deoxyribonucleic acid strand breaks. J Biol Chem 1983; 258:711–713.
Demple B, DeMott MS. Dynamics and diversions in base excision DNA repair of oxidized abasic lesions. Oncogene 2002; 21:8926–8934.
Ward JF. Complexity of damage produced by ionizing radiation. Cold Spring Harb Symp Quant Biol 2000; 65:377–382.
Ward JF, Milligan JR. Four mechanisms for the production of complex damage. Radiat Res 1997; 148:481–522.
Lindahl T. Instability and decay of the primary structure of DNA. Nature 1993; 362:709–715.
Kamath-Loeb AS, Hizi A, Kasai H et al. Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by reverse transcriptases and mammalian DNA polymerases. J Biol Chem 1997; 272:5892–5898.
Miller H, Prasad R, Wilson SH et al. 8-OxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279. Biochemistry 2000; 39:1029–1033.
Dedon PC, Goldberg IH. Free-radical mechanisms involved in the formation of sequence-dependent bistranded DNA lesions by the antitumor antibiotics bleomycin, neocarzinostatin, and calicheamicin. Chem Res Toxicol 1992; 5:311–332.
Hazra TK, Izumi T, Boldogh I et al. Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. Proc Natl Acad Sci USA 2002; 99:3523–3528.
Inamdar KV, Pouliot JJ, Zhou T et al. Conversion of phosphoglycolate to phosphate termini on 3′ overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1. J Biol Chem 2002; 277:27162–27168.
Parsons JL, Dianova II, Allinson SL et al. Poly(ADP-ribose) polymerase-1 protects excessive DNA strand breaks from deterioration during repair in human cell extracts. FEBS J 2005; 272:2012–2021.
Allinson SL, Dianova II, Dianov GL. Poly(ADP-ribose) polymerase in base excision repair: Always engaged, but not essential for DNA damage processing. Acta Biochim Pol 2003; 50:169–179.
Vodenicharov MD, Sallmann FR, Satoh MS et al. Base excision repair is efficient in cells lacking poly(ADP-ribose) polymerase 1. Nucl Acids Res 2000; 28:3887–3896.
Caldecott KW, Aoufouchi S, Johnson P et al. XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular ‘nick-sensor’ in vitro. Nucl Acids Res 1996; 24:4387–4394.
Nash RA, Caldecott KW, Barnes DE et al. XRCC1 protein interacts with one of two distinct forms of DNA ligase III. Biochemistry 1997; 36:5207–5211.
Cappelli E, Taylor R, Cevasco M et al. Involvement of XRCC1 and DNA ligase III gene products in DNA base excision repair. J Biol Chem 1997; 272:23970–23975.
Caldecott KW. XRCC1 and DNA strand break repair. DNA Repair (Amst) 2003; 2:955–969.
Demple B, Herman T, Chen DS. Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: Definition of a family of DNA repair enzymes. Proc Natl Acad Sci USA 1991; 88:11450–11454.
Robson CN, Hickson ID. Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants. Nucl Acids Res 1991; 19:5519–5523.
Meira LB, Devaraj S, Kisby GE et al. Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress. Cancer Res 2001; 61:5552–5557.
Ludwig DL, MacInnes MA, Takiguchi Y et al. A murine AP-endonuclease gene-targeted deficiency with post-implantation embryonic progression and ionizing radiation sensitivity. Mutat Res 1998; 409:17–29.
Xanthoudakis S, Smeyne RJ, Wallace JD et al. The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice. Proc Natl Acad Sci USA 1996; 93:8919–8923.
Ramana CV, Boldogh I, Izumi T et al. Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals. Proc Natl Acad Sci USA 1998; 95:5061–5066.
Grosch S, Fritz G, Kaina B. Apurinic endonuclease (Ref-1) is induced in mammalian cells by oxidative stress and involved in clastogenic adaptation. Cancer Res 1998; 58:4410–4416.
Silber JR, Bobola MS, Blank A et al. The apurinic/apyrimidinic endonuclease activity of Apel/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin Cancer Res 2002; 8:3008–3018.
Fung H, Demple B. A vital role for Apel/Ref1 protein in repairing spontaneous DNA damage in human cells. Mol Cell 2005; 17:463–470.
Wilson DM, Barsky D. The major human abasic endonuclease: Formation, Consequences and repair of abasic lesions in DNA. Mutat Res 2001; 485:283–307.
Chen D, Herman T, Demple B. Two distinct human DNA diesterases that hydrolyze 3′-blocking deoxyribose fragments from oxidized DNA. Nucl Acids Res 1991; 19:5907–5914.
Wiederhold L, Leppard JB, Kedar P et al. AP endonuclease-independent DNA base excision repair in human cells. Mol Cell 2004; 15:209–220.
Chaudhry MA, Dedon PC, WilsonIII DM et al. Removal by human apurinic/apyrimidinic endonuclease 1 (Ape 1) and Escherichia coli exonuclease III of 3′-phosphoglycolates from DNA treated with neocarzinostatin, calicheamicin, and [gamma]-radiation. Biochem Pharmacol 1999; 57:531–538.
Wilson DM. Properties of and substrate determinants for the exonuclease activity of human apurinic endonuclease Apel. J Mol Biol 2003; 330:1027–1037.
Kane C, Linn S. Purification and characterization of an apurinic/apyrimidinic endonuclease from HeLa cells. J Biol Chem 1981; 256:3405–3414.
Xu YJ, Kim EY, Demple B. Excision of C-4′-oxidized deoxyribose lesions from double-stranded DNA by human apurinic/apyrimidinic endonuclease (Apel protein) and DNA polymerase beta. J Biol Chem 1998; 273:28837–28844.
Winters T, Henner W, Russell P et al. Removal of 3′-phosphoglycolate from DNA strand-break damage in an oligonucleotide substrate by recombinant human apurinic/apyrimidinic endonuclease 1. Nucl Acids Res 1994; 22:1866–1873.
Izumi T, Hazra TK, Boldogh I et al. Requirement for human AP endonuclease 1 for repair of 3′-blocking damage at DNA single-strand breaks induced by reactive oxygen species. Carcinogenesis 2000; 21:1329–1334.
Suh D, Wilson DM, Povirk LF. 3′-phosphodiesterase activity of human apurinic/apyrimidinic endonuclease at DNA double-strand break ends. Nucl Acids Res 1997; 25:2495–2500.
Parsons JL, Dianova II, Dianov GL. APE1 is the major 3′-phosphoglycolate activity in human cell extracts. Nucl Acids Res 2004; 32:3531–3536.
Chou KM, Cheng YC. An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3′ mispaired DNA. Nature 2002; 415:655–659.
Parsons JL, Dianova II, Dianov GL. APE1-dependent repair of DNA single-strand breaks containing 3′-end 8-oxoguanine. Nucl Acids Res 2005; 33:2204–2209.
Vidal AE, Boiteux S, Hickson ID et al. XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J 2001; 20:6530–6539.
Jilani A, Ramotar D, Slack C et al. Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3′-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage. J Biol Chem 1999; 274:24176–24186.
Karimi-Busheri F, Daly G, Robins P et al. Molecular characterization of a human DNA kinase. J Biol Chem 1999; 274:24187–24194.
Bernstein NK, Williams RS, Rakovszky ML et al. The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase. Mol Cell 2005; 17:657–70.
Meijer M, Karimi-Busheri F, Huang TY et al. Pnk1, a DNA kinase/phosphatase required for normal response to DNA damage by gamma-radiation or camptothecin in Schizosaccharomyces pombe. J Biol Chem 2002; 277:4050–4055.
Whitehouse CJ, Taylor RM, Thistlethwaite A et al. XCCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 2001; 104:107–117.
Chappell C, Hanakahi LA, Karimi-Busheri F et al. Involvement of human polynucleotide kinase in double-strand break repair by nonhomologous end joining. EMBO J 2002; 21:2827–2832.
Koch CA, Agyei R, Galicia S et al. XRCC4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV. EMBO J 2004; 23:3874–3885.
Rasouli-Nia A, Karimi-Busheri F, Weinfeld M. Stable downregulation of human polynucleotide kinase enhances spontaneous mutation frequency and sensitizes cells to genotoxic agents. Proc Natl Acad Sci USA 2004; 101:6905–6910.
Yang SW, Burgin Jr AB, Huizenga BN et al. A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases. Proc Natl Acad Sci USA 1996; 93:11534–11539.
Suh D, Wilson IIIrd DM, Povirk LF. 3′-phosphodiesterase activity of human apurinic/apyrimidinic endonuclease at DNA double-strand break ends. Nucl Acids Res 1997; 25:2495–2500.
Zhou T, Lee JW, Tatavarthi H et al. Deficiency in 3′-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1). Nucl Acids Res 2005; 33:289–297.
Takashima H, Boerkoel CF, John J et al. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat Genet 2002; 32:267–272.
Guzder SN, Torres-Ramos C, Johnson RE et al. Requirement of yeast Rad1–Rad10 nuclease for the removal of 3′-blocked termini from DNA strand breaks induced by reactive oxygen species. Genes Dev 2004; 18:2283–2291.
El-Khamisy SF, Saifi GM, Weinfeld M et al. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature 2005; 434:108–113.
Brenner C, Hint, Fhit, and Galt: Function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. Biochemistry 2002; 41:9003–9014.
Moreira MC, Barbot C, Tachi N et al. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat Genet 2001; 29:189–193.
Date H, Igarashi S, Sano Y et al. The FHA domain of aprataxin interacts with the C-terminal region of XRCC1. Biochem Biophys Res Commun 2004; 325:1279–1285.
Caldecott KW. DNA single-strand break repair and spinocerebellar ataxia. Cell 2003; 112:7–10.
Gueven N, Becherel OJ, Kijas AW et al. Aprataxin, a novel protein that protects against genotoxic stress. Hum Mol Genet 2004; 13:1081–1093.
Clements PM, Breslin C, Deeks ED et al. The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amst) 2004; 3:1493–1502.
Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11:1513–1530.
Qu T, Morimoto K. X-ray repair cross-complementing group 1 polymorphisms and cancer risks in asian populations: A mini review. Cancer Detect Prev 2005; 29:215–220.
Hu JJ, Smith TR, Miller MS et al. Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Environ Mol Mutagen 2002; 39:208–215.
Zhou W, Liu G, Miller DP et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2003; 12:359–365.
Sturgis EM, Castillo EJ, Li L et al. Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck. Carcinogenesis 1999; 20:2125–2129.
Xing D, Qi J, Miao X et al. Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. Int J Cancer 2002; 100:600–605.
Ratnasinghe D, Yao SX, Tangrea JA et al. Polymorphisms of the DNA repair gene ERCC1 and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2001; 10:119–123.
Hu JJ, Smith TR, Miller MS et al. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 2001; 22:917–922.
Shen M, Berndt SI, Rothman N et al. Polymorphisms in the DNA base excision repair genes APEX1 and XRCC1 and lung cancer risk in Xuan Wei, China. Anticancer Res 2005; 25:537–542.
NIEHS-SNPs. NIEHS environmental genome project, NIEHS ES15478, department of genome sciences. Seattle: University of Washington, (URL: http://egp.gs.washington.edu). Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
Livingston RJ, von Niederhausern A, Jegga AG et al. Pattern of sequence variation across 213 environmental reponse genes. Genome Res 2004; 14:1821–1831.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Parsons, J.L., Boswell, E., Dianov, G.L. (2007). Processing of 3′-End Modified DNA Strand Breaks Induced by Oxidative Damage. In: Evans, M.D., Cooke, M.S. (eds) Oxidative Damage to Nucleic Acids. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72974-9_6
Download citation
DOI: https://doi.org/10.1007/978-0-387-72974-9_6
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-72973-2
Online ISBN: 978-0-387-72974-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)