Two Mechanisms Produce Mutation Hotspots at DNA Breaks in Escherichia coli
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Mutation hotspots and showers occur across phylogeny and profoundly influence genome evolution, yet the mechanisms that produce hotspots remain obscure. We report that DNA double-strand breaks (DSBs) provoke mutation hotspots via stress-induced mutation in Escherichia coli. With tet reporters placed 2 kb to 2 Mb (half the genome) away from an I-SceI site, RpoS/DinB-dependent mutations occur maximally within the first 2 kb and decrease logarithmically to ∼60 kb. A weak mutation tail extends to 1 Mb. Hotspotting occurs independently of I-site/tet-reporter-pair position in the genome, upstream and downstream in the replication path. RecD, which allows RecBCD DSB-exonuclease activity, is required for strong local but not long-distance hotspotting, indicating that double-strand resection and gap-filling synthesis underlie local hotspotting, and newly illuminating DSB resection in vivo. Hotspotting near DSBs opens the possibility that specific genomic regions could be targeted for mutagenesis, and could also promote concerted evolution (coincident mutations) within genes/gene clusters, an important issue in the evolution of protein functions.
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These data support previous work showing that increases in the mutation rate following DNA damage are due to the action of specific repair machinery, rather than the DNA damage itself.
“These data support previous work showing that increases in the mutation rate following DNA damage are due to the action of specific repair machinery, rather than the DNA damage itself (57–60).”
From Staphylococcus aureus Adapts to Oxidative Stress by Producing H <sub>2</sub> O <sub>2</sub> -Resistant Small-Colony Variants via the SOS Response (2015) · cites this paper as [60]
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- Authors
- Shee, C., Gibson, J. L., & Rosenberg, S. M.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Rosenberg, Susan M.
- ORCID
- Rosenberg, Susan M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 2
- Issue
- 4
- Pages
- 714-721
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC3607216
- OpenAlex
- W2073156372
- Cited by
- 68
- References
- 62
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 4 · 2016: 9 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Cancer Institute (DP1CA174424)
- National Institute of General Medical Sciences (R01GM53158, R01GM053158)
- 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
- mutational hotspots, DNA double-strand breaks, Escherichia coli, RecD, concerted evolution, genome evolution
- MeSH terms
- Bacterial Proteins, DNA Repair, Escherichia coli, Mutation, Sigma Factor, Genes, Reporter, Escherichia coli Proteins, Exodeoxyribonuclease V, DNA Breaks, Double-Stranded
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