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Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks
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Mechanisms of DNA repair and mutagenesis are defined on the basis of relatively few proteins acting on DNA, yet the identities and functions of all proteins required are unknown. Here, we identify the network that underlies mutagenic repair of DNA breaks in stressed Escherichia coli and define functions for much of it. Using a comprehensive screen, we identified a network of ≥93 genes that function in mutation. Most operate upstream of activation of three required stress responses (RpoS, RpoE, and SOS, key network hubs), apparently sensing stress. The results reveal how a network integrates mutagenic repair into the biology of the cell, show specific pathways of environmental sensing, demonstrate the centrality of stress responses, and imply that these responses are attractive as potential drug targets for blocking the evolution of pathogens.
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“Research on carbon-starved E. coli populations has shown that stress responses are required for the mutagenic repair of DNA breaks [75].”
From DNA Data Storage. (2023) · cites this paper as [75]
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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 (57–60).”
From Staphylococcus aureus Adapts to Oxidative Stress by Producing H 2 O 2 -Resistant Small-Colony Variants via the SOS Response (2015) · cites this paper as [57]
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Metadata
- Authors
- Al Mamun, A. A. M., Lombardo, M.-J., Shee, C., Lisewski, A. M., Gonzalez, C., Lin, D., Nehring, R. B., Saint-Ruf, C., Gibson, J. L., Frisch, R. L., Lichtarge, O., Hastings, P. J., & Rosenberg, S. M.
- Affiliations
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030–3411, USA.
- Baylor College of Medicine (US)
- U1001 INSERM, Université Paris, Descartes, Sorbonne Paris cité, site Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
- Corresponding author
- Lombardo, Mary-Jane
- Shee, Chandan
- Rosenberg, Susan M.
- ORCID
- Venue
- Science
- Published
- 2012-12-07
- Volume
- 338
- Issue
- 6112
- Pages
- 1344-1348
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3782309
- OpenAlex
- W2048699088
- Cited by
- 224
- References
- 133
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 15 · 2023: 22 · 2022: 10 · 2021: 10 · 2020: 15 · 2019: 17 · 2018: 11 · 2017: 27 · 2016: 22 · 2015: 20 · 2014: 21 · 2013: 17
- FWCI
- 11.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Cancer Institute (DP1CA174424)
- National Institute of General Medical Sciences (GM66099, F32GM019909, F32-GM19909, R01GM53158, R01GM064022, R25GM056929, R01GM066099, R01GM053158, R01GM079656, F32GM095267, R01-GM64022, GM79656)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- DNA repair, mutagenesis, DNA strand breaks, Escherichia coli, gene networks, RpoS, RpoE, SOS response, stress response, environmental sensing, therapeutic target, pathogen evolution
- MeSH terms
- Bacterial Proteins, DNA Repair, Escherichia coli, Sigma Factor, SOS Response, Genetics, Stress, Physiological, Gene Expression Regulation, Bacterial, Mutagenesis, Gene Regulatory Networks, DNA Breaks, Double-Stranded
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