Mismatch repair protein MutL becomes limiting during stationary-phase mutation

Reuben S. Harris, Gang Feng, Kimberly J. Ross, Roger Sidhu, Carl Thulin, Simonne Longerich, Susan K. Szigety, Malcolm E. Winkler, Susan M. Rosenberg

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2426-2437
Number of pages12
JournalGenes and Development
Volume11
Issue number18
DOIs
StatePublished - Sep 15 1997
Externally publishedYes

Keywords

  • Adaptive mutation
  • Evolution
  • Genetic instability
  • Mismatch repair
  • Mutation
  • MutL
  • Stationary phase

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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