Seven mutants of Escherichia coli were isolated that are sensitive to methyl methane sulfonate but not to UV light. They exhibited decreased host cell reactivation capacity for methyl methane sulfonate-treated phage X. Five of the mutations were mapped in the same region as alkA (previously called alk) and may indeed be identical to known mutations. Another mutation was found near nalA, and the gene responsible was named,alkB. Its phenotype was different from that of

A new type of Escherichia coli mutant which shows increased sensitivity to methyl methane sulfonate but not to UV light or to gamma rays was isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The mutant is unable to reactivate phage Avir or double-stranded 4X174 DNA (replicative form) that had been treated with methyl methane sulfonate. The mutant is sensitive to other alkylating agents, such as ethyl methane sulfonate, mitomycin C, and Nmethyl-N'-nitro-N-nitrosoguanidine, as well. It grows normally and exhibits almost normal recombination proficiency. The mutant possesses normal levels of DNA polymerase I, exonuclease I, exonuclease V, endonuclease specific for methyl methane sulfonate-treated DNA, and 3-methyladenine-DNA glycosidase activities. The genetic locus responsible has been named alk and is located near his on the chromosome.

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A strain with both the polA12 and the alk-1 mutation is only slightly more sensitive to methyl methane sulfonate (MMS) than isogenic strains with only one of the mutations. On the other hand, alk-1 recA1 double mutant is much more sensitive to MMS than are strains carrying either one of alk or recA mutation. It was suggested that the alk and the polA gene products are involved in the same DNA repair process whereas the recA function is independent from the process. The yield of MMS-induced mutation (Arg- (argE) to Arg+ reversion) in alk mutant is considerably higher than that in wild type strain. Thus, the repair process in which the alk gene product is involved is relatively accurate. When MMS-treated lambda phages were plated on MMS-treated bacteria, there were considerable increases in survival of treated phage even in recA alk double mutant. It seems that a new repair pathway, which is specific for alkylating agent-induced damages and is not dependent on the RecA function, may be induced on exposure of bacteria to the alkylating agent.