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Science 338 (6112): 1344-1348

Copyright © 2012 by the American Association for the Advancement of Science

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

Abu Amar M. Al Mamun,1 Mary-Jane Lombardo,1,*,{dagger} Chandan Shee,1,* Andreas M. Lisewski,1 Caleb Gonzalez,1,{ddagger} Dongxu Lin,1,§ Ralf B. Nehring,1 Claude Saint-Ruf,2,|| Janet L. Gibson,1 Ryan L. Frisch,1 Olivier Lichtarge,1,3 P. J. Hastings,1 Susan M. Rosenberg1,3,4,5

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.

1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030–3411, USA.
2 U1001 INSERM, Université Paris, Descartes, Sorbonne Paris cité, site Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
3 Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
4 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
5 The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

* These authors contributed equally to this work.

{dagger} Present address: Seres Health, Inc., 1 Memorial Drive, Cambridge, MA 02142, USA.

{ddagger} Present address: Department of Systems Biology (Unit 950), University of Texas M.D. Anderson Cancer Center, 7435 Fannin Street, Houston, TX 77054, USA.

§ Present address: Department of Cell Biology, Yale University, 333 Cedar Street, New Haven, CT 06520, USA.

|| Present address: U1001 INSERM, Université Paris Descartes, Sorbonne Paris Cité, Site Cochin, 24 rue du Faubourg St. Jacques, 75014 Paris, France.

To whom correspondence should be addressed. E-mail: smr{at}bcm.edu


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