Spectra of spontaneous mutations in Escherichia coli strains defective in mismatch correction: the nature of in vivo DNA replication errors

Proc Natl Acad Sci U S A. 1987 Sep;84(17):6220-4. doi: 10.1073/pnas.84.17.6220.

Abstract

We have determined the DNA sequence changes in 487 spontaneous mutations in the N-terminal part of the lacI gene in mutH, mutL, and mutS strains of Escherichia coli. These strains display elevated spontaneous mutation rates because of a deficiency in the process of postreplicative mismatch correction. As a consequence the mutational spectra reveal the nature of spontaneous DNA replication errors. The spectra consist of base substitutions (75%) and single-base deletions (25%). Among the base substitutions, transitions (both A.T----G.C and G.C----A.T) are strongly favored over transversions (96% versus 4%). Large site-to-site differences are observed among identical base substitutions, presumably reflecting the modulating effects of neighboring bases. The single-base-deletion spectrum is dominated by a large hotspot at a run of adjacent identical base pairs, implying a Streisinger-slippage mechanism. The data, when compared to a previously determined wild-type spectrum, also provide information on the specificity of the mismatch repair system.

MeSH terms

  • Base Sequence
  • Chromosome Deletion
  • DNA Repair
  • DNA Replication*
  • DNA, Bacterial / biosynthesis
  • DNA, Bacterial / genetics
  • Escherichia coli / genetics*
  • Mutation*

Substances

  • DNA, Bacterial