A mutation in the DNA adenine methylase gene ( dam) of Salmonella typhimurium decrease susceptibility to 9-aminoacridine-induced frameshift mutagenesis

Abstract

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-aminopourine(2AP) intermediate between that of the dam + and the DNA adenine methylation-decifit dam-1 strain, and 2AP sensitivity was reversed by introduction of a muH mutation or 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 induced equivalent levels of frameshift mutagnesis 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 mutation, 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-receptor 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. Futhermore, addition of methione to the assay medium reverses the 2AP sensitivity of the dam-2 strain, but has no effect on 9AA mutaganesis.