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Department of Biochemistry, University of Alberta Faculty of
Medicine, Edmonton, Alberta T6G 2H7 Canada;
2 Department of
Microbiology and Molecular Genetics, University of Texas Houston
Medical School, Houston, Texas 77030-1501 USA
Postsynthesis mismatch repair is an important contributor to
mutation avoidance and genomic stability in bacteria, yeast, and
humans. Regulation of its activity would allow organisms to regulate
their ability to evolve. That mismatch repair might be down-regulated
in stationary-phase Escherichia coli was suggested by the
sequence spectrum of some stationary-phase ("adaptive") mutations
and by the observations that MutS and MutH levels decline during
stationary phase. We report that overproduction of MutL inhibits
mutation in stationary phase but not during growth. MutS overproduction
has no such effect, and MutL overproduction does not prevent
stationary-phase decline of either MutS or MutH. These results imply
that MutS and MutH decline to levels appropriate for the decreased DNA
synthesis in stationary phase, whereas functional MutL is limiting for
mismatch repair specifically during stationary 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 pathogenicity, and the
origins of cancer.
[Key Words: Mismatch repair; MutL; mutation; adaptive mutation; genetic instability; evolution; stationary phase]
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