An aerobic recA-, umuC-dependent pathway of spontaneous base-pair substitution mutagenesis in Escherichia coli

Antimutator alleles indentify genes whose normal products are involved in s pontaneous mutagenesis pathways. Mutant alleles of the recA and umuC genes of Escherichia coli. whose wild-type alleles are components of the inducibl e SOS response, were shown to cause a decrease in the level of spontaneous mutagenesis. Using a series of chromosomal mutant trp alleles, which detect point mutations, as a reversion assay, it was shown that the reduction in mutagenesis is limited to base-pair substitutions. Within the limited numbe r of sites than could be examined, transversions at AT sites were the favor ed substitutions. Frameshift mutagenesis was slightly enhanced by a mutant recA allele and unchanged by a mutant umuC allele, The wild-type recA and u muC genes are involved in the same mutagenic base-pair substitution pathway , designated "SOS-dependent spontaneous mutagenesis" (SDSM), since a recAum uC strain showed the same degree and specificity of antimutator activity as either single mutant strain. The SDSM pathway is active only in the presen ce of oxygen. since wild-type, recA, and umuC strains all show the same lev els of reduced spontaneous mutagenesis anaerobically. The SDSM pathway can function in starving/stationary cells and may. or may not, be operative in actively dividing cultures, we suggest that, in wild-type cells, SDSM resul ts from basal levels of SOS activity during DNA synthesis. Mutations may re sult from synthesis past cryptic DNA lesions (targeted mutagenesis) and/or from mispairings during synthesis with a normal DNA template (untargeted mu tagenesis). Since it occurs in chromosomal genes of wild-type cells, SDSM m ay be biologically significant for isolates of natural enteric bacterial po pulations where extended starvation is often a common mode of existence. (C ) 2001 Elsevier Science B.V. All rights reserved.