Cited by 68DNA Repair MechanismsBacterial Genetics and BiotechnologyEvolution and Genetic Dynamics

Two Mechanisms Produce Mutation Hotspots at DNA Breaks in Escherichia coli

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Shee, Chandan, Gibson, Janet L., Rosenberg, Susan M.·2012·Cell Reports

Abstract

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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  1. Dillingham, M.S., and Kowalczykowski, S.C. (2008). RecBCD enzyme and the repair of double-stranded DNA breaks. Microbiol. Mol. Biol. Rev. 72, 642–671. PMC2593567 19052323
  2. Gumbiner-Russo, L.M., Lombardo, M.-J., Ponder, R.G., and Rosenberg, S.M. (2001). The TGV transgenic vectors for single-copy gene expression from the Escherichia coli chromosome. Gene 273, 97–104. 11483365
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  7. Shee, C., Gibson, J.L., Darrow, M.C., Gonzalez, C., and Rosenberg, S.M. (2011). Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli. Proc. Natl. Acad. Sci. USA 108, 13659–13664. PMC3158223 21808005

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Authors
Shee, C., Gibson, J. L., & Rosenberg, S. M.
Affiliations
Baylor College of Medicine (US)
Corresponding author
Rosenberg, Susan M.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2012-10
Volume
2
Issue
4
Pages
714-721
ISSN
2211-1247 (ISSN-L)
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
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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