The influence of the mismatch-repair system on stationary-phase mutagenesis in the yeast Saccharomyces cerevisiae

Stationary-phase (also called adaptive) mutation occurs in non-dividing cells during prolonged non-lethal selective pressure, e.g. starvation for an essential amino acid. Because in such conditions no DNA replication is observed, mutations probably arise as a result of inefficient DNA repair. In order to understand the role of the yeast mismatch-repair (MMR) system in the mutagenesis of stationary-phase cells, we studied the effects of deletions in genes encoding MutS- and MutL-related proteins on the reversion frequency of the lys2DeltaBgl frameshift mutation. We found that the level of Lys(+) reversion was increased in all MMR mutants, with the strongest effect observed in a MSH2 (MUTS homologue)-deprived strain. Disruption of the MSH3 or MSH6 genes (also MUTS homologues) resulted in elevation of the mutation frequency and rate, but to a lesser degree than that caused by the inactivation of MSH2. MutL-related proteins were also required for mutation avoidance in stationary-phase cells, but to a lesser extent than MutS homologues. Among MutL homologues, Mlh1 seems to play the major role in this process, while Pms1 and Mlh3 are partially redundant and appear to substitute for each other. These data suggest that MMR proteins, particularly MutS homologues, are involved in the control of mutability in stationary-phase yeast cells.