AlkB dioxygenase in preventing MMS-induced mutagenesis in Escherichia coli: Effect of Pol V and AlkA proteins

The deleterious effect of defective alkB allele encoding 1 meA/3 meC dioxygenase on reactivation of MMS-treated phage DNA has been frequently studied. Here, it is shown that: (i) AlkB protects the cells not only against the genotoxic but also against the potent mutagenic activity of MMS; (ii) mutations arising in alkB-defected strains are umuDC-dependent, and deletion of umuDC dramatically reduce MMS-induced mutations resulting from the presence of 1 meA/3 meC in DNA; (iii) specificity of MMS-induced argE3 → Arg+ reversions in AB1157 alkB-defective cells are predominantly AT → TA transversions and GC → AT transitions; (iv) overproduction of AlkA and the resultant decrease in 3 meA residues in DNA dramatically reduce MMS-induced mutations. This reduction is most probably a secondary effect of AlkA due to a decrease in 3 meA residues in DNA and, in consequence, suppression of SOS induction and Pol V expression. Overproduction of UmuD′C proteins reverses this effect.