MISMATCH REPAIR PROTEIN MUTL BECOMES LIMITING DURING STATIONARY-PHASEMUTATION

Postsynthesis mismatch repair is an important contributor to mutation avoidance and genomic stability in bacteria, yeast, and humans. Regula tion of its activity would allow organisms to regulate their ability t o evolve. That mismatch repair might be down-regulated in stationary-p hase Escherichia coli was suggested by the sequence spectrum of some s tationary-phase (''adaptive'') mutations and by the observations that MutS and MutH levels decline during stationary phase. We report that o verproduction of MutL inhibits mutation in stationary phase but not du ring growth. MutS overproduction has no such effect, and MutL overprod uction does not prevent stationary-phase decline of either MutS or Mut H. These results imply that MutS and MutH decline to levels appropriat e for the decreased DNA synthesis in stationary phase, whereas functio nal MutL is Limiting for mismatch repair specifically during stationar y phase. Modulation of mutation rate and genetic stability in response to environmental or developmental cues, such as stationary phase and stress, could be important in evolution, development, microbial pathog enicity, and the origins of cancer.