Effect of Escherichia coli dnaE antimutator mutants on mutagenesis by the base analog N4-aminocytidine.
Previous studies in our laboratory have identified a set of mutations in the Escherichia coli dnaE gene that confer increased accuracy of DNA replication (antimutators). The dnaE gene encodes the polymerase subunit of DNA polymerase III holoenzyme that replicates the E. coli chromosome. Here, we have investigated their effect on mutagenesis by the base analog N4-aminocytidine (4AC). For three different mutational markers, rifampicin resistance, nalidixic acid resistance and lacI forward mutagenesis, the dnaE911 allele reduced 4AC-induced mutagenesis by approximately 2.5-fold, while the dnaE915 allele reduced it by 2.5-, 3.5- and 6.5-fold, respectively. We also investigated the dependence of 4AC mutagenesis on mutations in the MutHLS mismatch repair system and the UvrABC nucleotide excision repair system. The results show that mutagenesis by 4AC is unaffected by defects in either system. The combined results point to the critical role of the DNA polymerase in preventing mutations by base analogs.
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. schaaper@niehs.nih.gov
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D000483:Alleles; D016587:Antimutagenic Agents; D002876:Chromosomes, Bacterial; D003562:Cytidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004258:DNA Polymerase III / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics*; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation
D016587:Antimutagenic Agents; D009153:Mutagens; C038769:N(4)-aminocytidine; D003562:Cytidine; C074904:DNA polymerase III, alpha subunit; D004258:DNA Polymerase III