Effect of DNA-repair enzymes on mutagenesis by oxygen free radicals.
Cytosine to thymine transitions are among the most common types of mutations produced by oxygen damage to DNA. One possible mechanism for these transitions is deamination of cytosine to uracil. Using both a forward mutation assay as well as a reversion assay specific for damage to cytosines we show that direct deamination to uracil does not play a significant role in mutagenesis induced by reactive oxygen free radicals. In contrast, lesions sensitive to repair by E. coli endonuclease III play a major role in oxidative mutagenesis as evidenced by the ability of endonuclease III to modulate the extent of mutagenesis that results from exposure of DNA to oxygen free radicals.
Reid
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Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington School of Medicine, Seattle 98195.
Loeb
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D003596:Cytosine / Q000378:metabolism*; D045647:DNA Glycosylases; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D003641:Deamination; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004587:Electrophoresis, Agar Gel; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins; D005609:Free Radicals / Q000378:metabolism / Q000633:toxicity; D016296:Mutagenesis; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*; D012972:Sodium Hydroxide / Q000633:toxicity; D013379:Substrate Specificity; D051981:Uracil-DNA Glycosidase
D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; D005609:Free Radicals; D017382:Reactive Oxygen Species; D012972:Sodium Hydroxide; D003596:Cytosine; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase