Effect of Escherichia coli dnaE antimutator mutants on mutagenesis by the base analog N4-aminocytidine. 1998

R M Schaaper, and R L Dunn
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. schaaper@niehs.nih.gov

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.

UI MeSH Term Description Entries
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002876 Chromosomes, Bacterial Structures within the nucleus of bacterial cells consisting of or containing DNA, which carry genetic information essential to the cell. Bacterial Chromosome,Bacterial Chromosomes,Chromosome, Bacterial
D003562 Cytidine A pyrimidine nucleoside that is composed of the base CYTOSINE linked to the five-carbon sugar D-RIBOSE. Cytosine Ribonucleoside,Cytosine Riboside,Ribonucleoside, Cytosine,Riboside, Cytosine
D004258 DNA Polymerase III A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II. DNA Polymerase delta,DNA-Dependent DNA Polymerase III,DNA Pol III,DNA Dependent DNA Polymerase III,Polymerase III, DNA,Polymerase delta, DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D016587 Antimutagenic Agents Agents that reduce the frequency or rate of spontaneous or induced mutations independently of the mechanism involved. Anti-Mutagenic Agent,Antimutagen,Antimutagenic Agent,Anti-Mutagenic Agents,Anti-Mutagenic Effect,Anti-Mutagenic Effects,Antimutagenic Effect,Antimutagenic Effects,Antimutagens,Agent, Anti-Mutagenic,Agent, Antimutagenic,Agents, Anti-Mutagenic,Agents, Antimutagenic,Anti Mutagenic Agent,Anti Mutagenic Agents,Anti Mutagenic Effect,Anti Mutagenic Effects,Effect, Anti-Mutagenic,Effect, Antimutagenic,Effects, Anti-Mutagenic,Effects, Antimutagenic

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