A direct role for DNA polymerase III in adaptive reversion of a frameshift mutation in Escherichia coli

Reuben S. Harris; Harold J. Bull; Susan M. Rosenberg

doi:10.1016/S0027-5107(96)00244-8

A direct role for DNA polymerase III in adaptive reversion of a frameshift mutation in Escherichia coli

Reuben S. Harris, Harold J. Bull, Susan M. Rosenberg

Biochemistry, Molecular Biology, and Biophysics (CBS)

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

The sequences of adaptive reversions of a lac frameshift mutation in Escherichia coli resemble DNA polymerase errors, and the adaptive reversions decrease in strains with an antimutator DNA polymerase III (PolIII) allele. The latter finding could imply that DNA PolIII itself makes adaptive mutations. Alternatively, normal DNA PolIII errors could saturate post-synthesis mismatch repair during adaptive mutation. If so, the antimutator strain would produce fewer adaptive mutations because it possesses greater capacity for mismatch repair which could correct errors made by a polymerase other than DNA PolIII. Mismatch repair capacity is limited specifically during adaptive mutation, necessitating a test of this indirect model. This indirect model is ruled out here by the observation that the antimutator PolIII allele decreases adaptive mutation even in mismatch repair-defective cells. This supports a direct role for DNA PolIII in recombination-dependent adaptive mutation.

Original language	English (US)
Pages (from-to)	19-24
Number of pages	6
Journal	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume	375
Issue number	1
DOIs	https://doi.org/10.1016/S0027-5107(96)00244-8
State	Published - Apr 14 1997

Bibliographical note

Funding Information:
R.S.H. is enrolled in the graduate degree program of the Department of Biological Sciences, University of Alberta. We thank R. Schaaper for strains and helpful discussions, M.-J. Lombardo, P.J. Hastings and J. Torkelson for comments on the manuscript, and C. Thulin for excellent technical assistance. Supported by a grant from the National Cancer Institute of Canada, funded by the Canadian Cancer Society, a grant from the Public Health Service (USA), a graduate studentship from the Alberta Heritage Foundation for Medical Research (RSH) and an Honorary Izaak Walton Killam Memorial Scholarship (RSH). SMR is an Alberta Heritage Medical Scholar.

Keywords

Adaptive mutation
DNA polymerase III
Directed mutation
Escherichia coli
Mismatch repair
Recombination

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abstract = "The sequences of adaptive reversions of a lac frameshift mutation in Escherichia coli resemble DNA polymerase errors, and the adaptive reversions decrease in strains with an antimutator DNA polymerase III (PolIII) allele. The latter finding could imply that DNA PolIII itself makes adaptive mutations. Alternatively, normal DNA PolIII errors could saturate post-synthesis mismatch repair during adaptive mutation. If so, the antimutator strain would produce fewer adaptive mutations because it possesses greater capacity for mismatch repair which could correct errors made by a polymerase other than DNA PolIII. Mismatch repair capacity is limited specifically during adaptive mutation, necessitating a test of this indirect model. This indirect model is ruled out here by the observation that the antimutator PolIII allele decreases adaptive mutation even in mismatch repair-defective cells. This supports a direct role for DNA PolIII in recombination-dependent adaptive mutation.",

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N2 - The sequences of adaptive reversions of a lac frameshift mutation in Escherichia coli resemble DNA polymerase errors, and the adaptive reversions decrease in strains with an antimutator DNA polymerase III (PolIII) allele. The latter finding could imply that DNA PolIII itself makes adaptive mutations. Alternatively, normal DNA PolIII errors could saturate post-synthesis mismatch repair during adaptive mutation. If so, the antimutator strain would produce fewer adaptive mutations because it possesses greater capacity for mismatch repair which could correct errors made by a polymerase other than DNA PolIII. Mismatch repair capacity is limited specifically during adaptive mutation, necessitating a test of this indirect model. This indirect model is ruled out here by the observation that the antimutator PolIII allele decreases adaptive mutation even in mismatch repair-defective cells. This supports a direct role for DNA PolIII in recombination-dependent adaptive mutation.

AB - The sequences of adaptive reversions of a lac frameshift mutation in Escherichia coli resemble DNA polymerase errors, and the adaptive reversions decrease in strains with an antimutator DNA polymerase III (PolIII) allele. The latter finding could imply that DNA PolIII itself makes adaptive mutations. Alternatively, normal DNA PolIII errors could saturate post-synthesis mismatch repair during adaptive mutation. If so, the antimutator strain would produce fewer adaptive mutations because it possesses greater capacity for mismatch repair which could correct errors made by a polymerase other than DNA PolIII. Mismatch repair capacity is limited specifically during adaptive mutation, necessitating a test of this indirect model. This indirect model is ruled out here by the observation that the antimutator PolIII allele decreases adaptive mutation even in mismatch repair-defective cells. This supports a direct role for DNA PolIII in recombination-dependent adaptive mutation.

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KW - Mismatch repair

KW - Recombination

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A direct role for DNA polymerase III in adaptive reversion of a frameshift mutation in Escherichia coli

Abstract

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Keywords

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