ArticleNucleic acids research2020
Point mutations in topoisomerase I alter the mutation spectrum in E. coli and impact the emergence of drug resistance genotypes.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Extended sequence context shapes mutational bias inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrated omics reveal a unique antibacterial mechanism of action for the small molecule HSI#6.Current research in microbial sciences · 2026Article
- Role of DNA methylation transferase in urinary system diseases: From basic to clinical perspectives (Review).International journal of molecular medicine · 2025Review
- Physiologic and Transcriptomic Effects Triggered by Overexpression of Wild Type and Mutant DNA Topoisomerase I inInternational journal of molecular sciences · 2023Article
- Shifts in mutation spectra enhance access to beneficial mutations.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Genome-Wide Association Study of Nucleotide Variants Associated with Resistance to Nine Antimicrobials inMicroorganisms · 2022Article
- Article
- Mechanism of Type IA Topoisomerases.Molecules (Basel, Switzerland) · 2020Review
- Supercoiling, R-loops, Replication and the Functions of Bacterial Type 1A Topoisomerases.Genes · 2020Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identifying the molecular mechanisms that give rise to genetic variation is essential for the understanding of evolutionary processes. Previously, we have used adaptive laboratory evolution to enable biomass synthesis from CO2 in Escherichia coli. Genetic analysis of adapted clones from two independently evolving populations revealed distinct enrichment for insertion and deletion mutational events. Here, we follow these observations to show that mutations in the gene encoding for DNA topoisomerase I (topA) give rise to mutator phenotypes with characteristic mutational spectra. Using genetic assays and mutation accumulation lines, we find that point mutations in topA increase the rate of sequence deletion and duplication events. Interestingly, we observe that a single residue substitution (R168C) results in a high rate of head-to-tail (tandem) short sequence duplications, which are independent of existing sequence repeats. Finally, we show that the unique mutation spectrum of topA mutants enhances the emergence of antibiotic resistance in comparison to mismatch-repair (mutS) mutators, and leads to new resistance genotypes. Our findings highlight a potential link between the catalytic activity of topoisomerases and the fundamental question regarding the emergence of de novo tandem repeats, which are known modulators of bacterial evolution.
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