A mutation in the DNA adenine methylase gene (dam) of Salmonella typhimurium decreases susceptibility to 9-aminoacridine-induced frameshift mutagenesis.
A mutant of Salmonella typhimurium with a reduced response to mutation induction by 9-aminoacridine (9AA) has been isolated. The mutation (dam-2) is located in the DNA adenine methylase gene. The dam-2 mutant strain exhibits a level of sensitivity to 2-aminopurine (2AP) intermediate between that of the dam+ and the DNA adenine methylation-deficit dam-1 strain, and 2AP sensitivity was reversed by introduction of a mutH mutation or of the plasmid pMQ148 (which carries a functional Escherichia coli dam+ gene). However, the dam-2 strain is not grossly defective in DNA adenine methylase activity. Whole cell DNA appears full methylated at -GATC- sites. The levels of 9AA required to induce equivalent levels of frameshift mutagenesis in the dam-2 strain were approximately 2-fold higher than for the dam+ strain. Introduction of pMQ148 dam+ reduced the level of 9AA required for induction of frameshift mutations 4-fold in the dam-2 strain and 2-fold in the dam+ strain. The dam-2 mutation had no effect on the levels of ICR191 required for induction of frameshift mutations, but introduction of pMQ148 reduced the ICR191-induced mutagenesis 2-fold. The dam+/pMQ148, dam-2/pMQ148 and dam-1/pMQ148 strains showed identical dose-response curves for both 9AA and ICR191. These results are consistent with a slightly reduced (dam-2) or increased (pMQ148) rate of methylation at the replication fork. The 2AP sensitivity of the dam-2 strain cannot be simply explained. Furthermore, addition of methionine to the assay medium reverses the 2AP sensitivity of the dam-2 strain, but has no effect on 9AA mutagenesis.
Ritchie
L
L
CSIRO Division of Molecular Biology, North Ryde, NSW, Australia.
Podger
D M
DM
Hall
R M
RM
D000585:Aminacrine / Q000494:pharmacology*; D000609:Aminoacridines / Q000494:pharmacology*; D004251:DNA Transposable Elements; D005796:Genes; D005798:Genes, Bacterial; D005838:Genotype; D008780:Methyltransferases / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D013045:Species Specificity
D000609:Aminoacridines; D004251:DNA Transposable Elements; D000585:Aminacrine; D008780:Methyltransferases; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)