Mutagenesis and cellular responses to DNA damage.
Treatment of Escherichia coli with DNA-damaging agents results in the increased expression of a set of din (damage-inducible) genes. We have studied the regulation and function of these genes by using the Mud(Ap, lac) bacteriophage to obtain fusions of the beta-galactosidase structural gene to the promoters of various din genes. By this technique, we have shown that the uvrA, uvrB, and umuC genes are induced by UV and other DNA damaging agents. The products of the uvrA and uvrB genes are required for the excision repair of pyrimidine dimers and other bulky lesions; the umuC gene product is required for most chemical mutagenesis in E. coli. Genetic analyses of all of the din-lac fusions isolated to date indicate that lexA is the direct repressor of each of the din genes and that proteolytic cleavage of the lexA protein is required for their induction. We have also been studying the mechanism by which the clinically isolated plasmid pKM101 increases the susceptibility of cells to chemical mutagenesis. Inasmuch as the effects of pKM101 on mutagenesis are recA+ lexA+ -dependent and the plasmid can suppress the nonmutability of a umuC mutant, it seems likely that pKM101 may carry an analog of the chromosomal umuC gene. By insertion mutagenesis using Tn5, we identified an approximately 2,000-base pair region of pKM101 which is necessary for its effects on mutagenesis.
D001426:Bacterial Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003090:Coliphages / Q000235:genetics; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes; D005798:Genes, Bacterial; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D011815:R Factors; D011938:Rec A Recombinases; D011995:Recombination, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008937:Mitomycins; D009153:Mutagens; D016685:Mitomycin; D011938:Rec A Recombinases; D001616:beta-Galactosidase