EFFECT OF ESCHERICHIA-COLI DNAE ANTIMUTATOR MUTANTS ON MUTAGENESIS BYTHE BASE ANALOG N-4-AMINOCYTIDINE

Previous studies in our laboratory have identified a set of mutations in the Escherichia coli dnaE gene that confer increased accuracy of DN A replication (antimutators). The dnaE gene encodes the polymerase sub unit of DNA polymerase III holoenzyme that replicates the E. coli chro mosome. Here, we have investigated their effect on mutagenesis by the base analog N-4-aminocytidine (4AC). For three different mutational ma rkers, rifampicin resistance, nalidixic acid resistance and lad forwar d mutagenesis, the dnaE911 allele reduced 4AC-induced mutagenesis by a pproximately 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 mu tagenesis by 4AC is unaffected by defects in either system. The combin ed results point to the critical role of the DNA polymerase in prevent ing mutations by base analogs. (C) 1998 Elsevier Science B.V. All righ ts reserved.