The isfA mutation specifically inhibits the SOS-dependent mutagenic pathway and does not selectively affect any...

We have previously described a new mutation in Escherichia coli, isfA, which causes inhibition of SOS mutagenesis (UV-induced in rec+ and spontaneous in recA730 strains) and several SOS-dependent phenomena. Antimutagenic activity of the isfA mutation in the recA730 strain was shown to be related to inhibition of processing of UmuD to UmuD' by RecA* coprotease. In the present study we have analysed the specificity of the antimutagenic activity of the isfA mutation by employing F' plasmids carrying a set of mutant lacZ genes that can individually detect two types of transitions and four types of transversions. Analysis revealed that isfA inhibits UV-induced G:C-->A:T and A:T-->G:C transitions, but does not affect the same G:C-->A:T transitions induced by EMS, an SOS-independent mutagen. Analysis of the antimutagenic activity of the isfA mutation in two mutator strains, recA730 and mutL, showed that isfA inhibits SOS-dependent transversions in recA730, but not transitions generated as replication errors in the mutL strain. In the double mutant recA730 mutL, both transitions and transversions were enhanced and isfA inhibits most transversions and only those transitions generated by the recA730 mutation. The results indicate that the antimutagenic activity of the isfA mutation is specific for the SOS, UmuD'C-dependent mutagenic pathway but does not selectively affect any particular base substitution. Moreover, studies on the effect of the isfA mutation on transitions and transversions in different genetic backgrounds enable us to recognize different mutagenic pathways active in recA730 cells.