DNA methylation alters the pattern of spontaneous mutation in Escherichia coli cells (mutD) defective in DNA polymerase III proofreading.

We have shown previously that dam mutants of Escherichia coli have a weak mutator phenotype which generates mostly transition mutations in the P22 mnt gene. In contrast, in mutD5 cells, which have a strong mutator phenotype, transversion mutations were the most prevalent. A dam-16 mutD5 strain, defective in both DNA polymerase III associated-proofreading and Dam-directed mismatch repair exhibits a strong mutator phenotype but, surprisingly, its mutation spectrum is similar to that of the dam rather than the mutD parent. The most likely explanation is that Dam-directed mismatch repair in the mutD5 strain corrects most of the potential transition mutations (therefore yielding transversions) in the newly synthesised strand. When the dam-16 allele is present together with mutD5 a reduced efficiency of repair as well as loss of strand discrimination and misdirected repair results in the appearance of transition mutations at high frequency.