A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation
Open accessAbstract
Special mechanisms of mutation are induced in microbes under growth-limiting stress causing genetic instability, including occasional adaptive mutations that may speed evolution. Both the mutation mechanisms and their control by stress have remained elusive. We provide evidence that the molecular basis for stress-induced mutagenesis in an E. coli model is error-prone DNA double-strand break repair (DSBR). I-SceI-endonuclease-induced DSBs strongly activate stress-induced mutations near the DSB, but not globally. The same proteins are required as for cells without induced DSBs: DSBR proteins, DinB-error-prone polymerase, and the RpoS starvation-stress-response regulator. Mutation is promoted by homology between cut and uncut DNA molecules, supporting a homology-mediated DSBR mechanism. DSBs also promote gene amplification. Finally, DSBs activate mutation only during stationary phase/starvation but will during exponential growth if RpoS is expressed. Our findings reveal an RpoS-controlled switch from high-fidelity to mutagenic DSBR under stress. This limits genetic instability both in time and to localized genome regions, potentially important evolutionary strategies.
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C. albicans lab isolates likely undergo a stress-induced elevation of mutation and mitotic recombination rates.
“Third, C. albicans lab isolates likely undergo a stress-induced elevation of mutation and mitotic recombination rates (Ponder et al., 2005; Forche et al., 2011; Rosenberg, 2011)”
From The evolution of drug resistance in clinical isolates of Candida albicans. (2015) · cites this paper as Ponder et al., 2005
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- Authors
- Ponder, R. G., Fonville, N. C., & Rosenberg, S. M.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Rosenberg, Susan M.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 19
- Issue
- 6
- Pages
- 791-804
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2161319547
- Cited by
- 257
- References
- 77
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 11 · 2021: 12 · 2020: 10 · 2019: 16 · 2018: 13 · 2017: 12 · 2016: 14 · 2015: 11 · 2014: 12 · 2013: 18 · 2012: 24
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM53158, R01GM053158, T32GM008231)
- 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
- stress-induced mutagenesis, DNA double-strand break repair, error-prone DNA repair, RpoS, Escherichia coli, I-SceI endonuclease, gene amplification, genomic instability, adaptive mutation, starvation stress, stationary phase
- MeSH terms
- Base Sequence, DNA Damage, DNA Repair, DNA Helicases, Escherichia coli, Lac Operon, Molecular Sequence Data, Deoxyribonucleases, Type II Site-Specific, Mutagenesis, Point Mutation, Evolution, Molecular, Saccharomyces cerevisiae Proteins, Escherichia coli Proteins
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