Identity and function of a large gene network underlying mutagenic repair of DNA breaks.

TitleIdentity and function of a large gene network underlying mutagenic repair of DNA breaks.
Publication TypeJournal Article
Year of Publication2012
AuthorsMamun, AAmar MAl, Lombardo, M-J, Shee, C, Lisewski, AM, Gonzalez, C, Lin, D, Nehring, RB, Saint-Ruf, C, Gibson, JL, Frisch, RL, Lichtarge, O, Hastings, PJ, Rosenberg, SM
JournalScience
Volume338
Issue6112
Pagination1344-8
Date Published2012 Dec 7
ISSN1095-9203
KeywordsBacterial Proteins, DNA Breaks, Double-Stranded, DNA Repair, Escherichia coli, Gene Expression Regulation, Bacterial, Gene Regulatory Networks, Mutagenesis, Sigma Factor, SOS Response (Genetics), Stress, Physiological
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.

DOI10.1126/science.1226683
Alternate JournalScience
PubMed ID23224554
PubMed Central IDPMC3782309
Grant ListDP1 CA174424 / CA / NCI NIH HHS / United States
DP1-CA174424 / CA / NCI NIH HHS / United States
F32-GM095267 / GM / NIGMS NIH HHS / United States
F32-GM19909 / GM / NIGMS NIH HHS / United States
GM66099 / GM / NIGMS NIH HHS / United States
GM79656 / GM / NIGMS NIH HHS / United States
R01 GM053158 / GM / NIGMS NIH HHS / United States
R01 GM079656 / GM / NIGMS NIH HHS / United States
R01-GM53158 / GM / NIGMS NIH HHS / United States
R01-GM64022 / GM / NIGMS NIH HHS / United States