Spontaneous mutation in Escherichia coli containing the dnaE911 DNA polymerase antimutator allele
Open accessAbstract
We have previously isolated mutants of Escherichia coli that replicate their DNA with increased fidelity. These mutants have a mutation in the dnaE gene, encoding the alpha subunit of DNA polymerase III. They were isolated in a mismatch-repair-defective mutL background, in which mutations can be considered to represent uncorrected DNA replication errors. In the present study we analyze the effect of one of these alleles, dnaE911, on spontaneous mutagenesis in a mismatch-repair-proficient background. In this background, spontaneous mutations may be the sum of uncorrected replication errors and mutations resulting from other pathways. Hence, the effect of the dnaE allele may provide insights into the contribution of uncorrected DNA replication errors to spontaneous mutation. The data show that dnaE911 decreases the level of Rifr, lacI and galK mutations in this background by 1.5-2-fold. DNA sequencing of 748 forward mutants in the lacI gene reveals that this effect has a clear specificity. Transversions are decreased by approximately 3-fold, whereas transitions, frameshifts, deletions and duplications remain essentially unchanged. Among the transversions, A.T-->T.A are affected most strongly (approximately 6-fold). In addition to this effect on transversions within the lacI gene, one previously recognized A.T-->G.C base-pair substitution hotspot in the lac operator is also reduced (approximately 5-fold). The data are discussed in the light of the role of DNA replication errors in spontaneous mutation, as well as other possible explanations for the observed antimutator effects.
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In growing E. coli populations, mutants of the α subunit of replicative DNA polymerase III have been well characterized as antimutator alleles, suggesting that DNA replication errors are a major source of spontaneous mutagenesis under optimal growth conditions.
“In the growing E. coli population, mutants of the α subunit of replicative DNA polymerase III have been well characterized as antimutator alleles, suggesting that DNA replication errors are a major source of spontaneous mutagenesis under optimal growth conditions [76].”
From DNA Data Storage. (2023) · cites this paper as [76]
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- Authors
- Oller, A. R., & Schaaper, R. M.
- Affiliations
- National Institutes of Health (US)
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-10-01
- Volume
- 138
- Issue
- 2
- Pages
- 263-270
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W1913707695
- Cited by
- 33
- References
- 27
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2014: 4 · 2012: 2
- FWCI
- 0.51
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- DNA polymerase III alpha subunit, spontaneous mutagenesis, Escherichia coli, DNA replication errors, DNA mismatch repair, transversions, LacI, lac operator, rifampicin resistance, galK
- MeSH terms
- Base Sequence, DNA Polymerase III, Escherichia coli, Genes, Bacterial, Genes, Dominant, Genotype, Molecular Sequence Data, Mutation, Oligodeoxyribonucleotides, Frameshift Mutation, Point Mutation, Sequence Deletion
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