title: Hydrogen peroxide-induced microsatellite instability in the Escherichia coli K-12 endogenous tonB gene.
abstract: Damage to DNA by reactive oxygen species may be a significant source of endogenous mutagenesis in aerobic organisms. Using an endogenous tonB gene as a mutation selective marker in Escherichia coli, we have examined whether endogenous oxidative mutagenesis can contribute to genetic instability. We have also used oxyR(+) and oxyR(-) strains to evaluate how hydrogen peroxide scavenging system can contribute to genetic instability. The highest mutation frequency induced by hydrogen peroxide was 3.8x10(-6) at 600 microM and 5.3 x 10(-6) at 40 microM in oxyR(+) and oxyR(-), respectively. Hydrogen peroxide induced minus frameshift mutations predominantly followed by transversions (G:C-->T:A, G:C-->C:G, and A:T-->T:A). The types and the nature of the mutations did not differ between strains. Frameshift mutations occurred at G:C and A:T sites equally, and in repeated and non-repeated sequences equally. It is evident that endogenous oxidative damage to DNA can increase the frequency of strand slippage intermediates occurring during DNA replication and contribute to genomic instability. Our results further indicate that oxyR regulon does not take part in the DNA-repair pathway against oxidative damage induced by hydrogen peroxide.
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai 980-8577, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yamamura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nunoshiba
authors.forename: Takehiko
authors.initials: T
authors.lastname: Nohmi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D020137:Base Pair Mismatch; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D016368:Frameshift Mutation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008957:Models, Genetic; D016296:Mutagenesis; D009154:Mutation; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C499299:oxyR protein, E coli; C057616:tonB protein, Bacteria; C489181:tonB protein, E coli; D004247:DNA; D006861:Hydrogen Peroxide