MucAB but not UmuDC proteins enhance -2 frameshift mutagenesis induced by N-2-acetylaminofluorene at alternating GC sequences.

Abstract

N-2-acetylaminofluorene has been shown efficiently to induce both -1 and -2 frameshift mutations in Escherichia coli as well as in mammalian cells. In E. coli, the genetic characteristics of -1 and -2 frameshift mutations were found to be distinct. The -1 frameshift mutation pathway occurs at monotonous runs of G residues (i.e. GGG-->GG). This pathway exhibits the same genetic requirements as UV light-induced base substitution mutagenesis. Indeed, optimal mutagenesis requires the expression of both UmuDC and the activated form of RecA. The -2 frameshift mutation pathway operates at short alternating GpC sequences, such as the NarI sequence (i.e. GGCGCC-->GGCC). In contrast to the -1 frameshift mutation pathway, optimal induction does not require the UmuDC and RecA proteins. This pathway involves a LexA-repressed function tentatively called Npf (for NarI processing factor). In this paper, we show that MucAB efficiently stimulates the -2 frameshift mutation pathway. However, unlike the Npf pathway, MucAB-mediated stimulation requires expression of the RecA protein.