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

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Abstract
We have determined the DNA sequence changes in 487 spontaneous mutations in the N-terminal part of the lac1 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.cntdot.T .fwdarw. G.cntdot.C and G.cntdot.C .fwdarw. A.cntdot.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.