Mismatch correction at O6-methylguanine residues in E. coli DNA

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Department of Biochemistry and Molecular Pharmacology

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*DNA Repair; Escherichia coli; Guanine; Methylation; Methylnitronitrosoguanidine


Biochemistry, Biophysics, and Structural Biology


Escherichia coli has a correction system which removes mismatched bases from DNA1. Mutants (dam) which lack the major DNA adenine methylase2 are hypersensitive to the effects of base analogue mutagens such as 2-aminopurine3 and appear to be defective in mismatch correction. Phenotypic revertants of dam mutants to base analogue resistance include second site mutations in mutL or mutS genes4, which are also part of the correction system. We report here that E. coli dam mutants are also sensitive to the DNA methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which introduces O6-methylguanine (m6G) into the DNA. This sensitivity, however, was not observed using methylating agents which generate only low amounts of this alkylated base. Furthermore, the introduction of either a mutL or a mutS mutation into dam strains abolished the sensitivity to MNNG. These results suggest that mismatch correction occurs at m6G residues in DNA. These lesions miscode in DNA polymerase I-mediated DNA synthesis in vitro5 and are known to be mutagenic in vivo6. Nevertheless, it appears that mismatch correction at m6G residues in DNA does not lead to reduced induction of mutation by MNNG.


Nature. 1982 Apr 29;296(5860):868-9.

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