Widespread adaptive response against environmental methylating agents in microorganisms.

Many bacterial species have adaptive responses which protect against the toxicity and mutagenicity of methylating agents. Induced 3-methyladenine-DNA glycosylase and O6-methylguanine-DNA methyltransferase activities increase the cellular capacity of E. coli, B. subtilis, and M. luteus to repair toxic and mutagenic methylated base derivatives in DNA. The DNA methyltransferase or Ada protein of E. coli regulates the response and is converted into a strong transcriptional activator by self-methylation on repair of a methylphosphotriester in DNA. The multiple functions of the E. coli Ada protein (39 kDa) are split between two proteins, AdaA (24 kDa) and AdaB (20 kDa), in B. subtilis. Proteins (39 kDa) recognised by anti-Ada antibodies are efficiently induced in several enterobacterial species and correlate with increased DNA methyltransferase activities. In contrast, an "Ada-related" protein is only weakly induced in Salmonella typhimurium and no increase in DNA repair activity is detectable. The existence of adaptive responses in diverged bacterial species suggests the frequent occurrence of methylating agents in the environment. Several direct-acting methylating agents which are known to arise in the environment have been shown to induce the response. These include abundantly occurring methyl chloride, the antibiotic streptozotocin, the precursors of the known labile inducers N-methyl-N'-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine and as shown in this paper, methyl radicals which may arise by the irradiation or oxidation of methyl compounds.