title: Identity and function of a large gene network underlying mutagenic repair of DNA breaks.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411, USA.
authors.forename: Abu Amar M
authors.initials: AA
authors.lastname: Al Mamun
authors.forename: Mary-Jane
authors.initials: MJ
authors.lastname: Lombardo
authors.forename: Chandan
authors.initials: C
authors.lastname: Shee
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Lisewski
authors.forename: Caleb
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Dongxu
authors.initials: D
authors.lastname: Lin
authors.forename: Ralf B
authors.initials: RB
authors.lastname: Nehring
authors.forename: Claude
authors.initials: C
authors.lastname: Saint-Ruf
authors.forename: Janet L
authors.initials: JL
authors.lastname: Gibson
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Frisch
authors.forename: Olivier
authors.initials: O
authors.lastname: Lichtarge
authors.forename: P J
authors.initials: PJ
authors.lastname: Hastings
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rosenberg
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D016296:Mutagenesis / Q000235:genetics; D013014:SOS Response, Genetics / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; C063202:sporulation-specific sigma factors