Research Article Mutagenic Potency of MMS-Induced 1meA/3meC Lesions in E. coli

The mutagenic activity of MMS in E. coli depends on the susceptibility of DNA bases to methylation and their repair by cellular defense systems. Among the lesions in methylated DNA is 1meA/ 3meC, which is recently recognized as being muta-genic. In this report, special attention is focused on the mutagenic properties of 1meA/3meC which, by the activity of AlkB-dioxygenase, are quickly and efficiently converted to natural A/C bases in the DNA of E. coli alkB1 strains, preventing 1meA/ 3meC-induced mutations. We have found that in the absence of AlkB-mediated repair, MMS treat-ment results in an increased frequency of four types of base substitutions: GC?CG, GC?TA, AT?CG, and AT?TA, whereas overproduction of PolV in CC101–106 alkB2/pRW134 strains leads to a markedly elevated level of GC?TA, GC?CG, and AT?TA transversions. It has been observed that in the case of AB1157 alkB2 strains, the MMS-induced and 1meA/3meC-dependent argE3?Arg1 reversion occurs efficiently, whereas lacZ2? Lac1 reversion in a set of CC101–106 alkB2 strains occurs with much lower frequency. We considered several reasons for this discrep-ancy, namely, the possible variance in the level of the PolV activity, the effect of the PolIV contents that is higher in CC101–106 than in AB1157 strains and the different genetic cell backgrounds in CC101–106 alkB2 and AB1157 alkB2 strains, respectively. We postulate that the difference in the number of targets undergoing mutation and differ-ent reactivity of MMS with ssDNA and dsDNA are responsible for the high (argE3?Arg1) and low (lacZ2? Lac1) frequency of MMS—induced muta-tions. Environ. Mol. Mutagen. 50:791–799