Cited by 224Bacterial Genetics and BiotechnologyDNA Repair MechanismsFungal and yeast genetics research

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Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks

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Al Mamun, Abu Amar M., Lombardo, Mary-Jane, Shee, Chandan, Lisewski, Andreas M., Gonzalez, Caleb, Lin, Dongxu, Nehring, Ralf B., Saint-Ruf, Claude, Gibson, Janet L., Frisch, Ryan L., Lichtarge, Olivier, Hastings, P. J., Rosenberg, Susan M.·2012·Science

DOI 10.1126/science.1226683PMC PMC3782309

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Abstract

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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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: Lisewski, Andreas M.
Lin, Dongxu
Nehring, Ralf B.
Lichtarge, Olivier
Hastings, P. J.
Rosenberg, Susan M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2012-12-07
Volume: 338
Issue: 6112
Pages: 1344-1348
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1226683
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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Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks

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