Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

Combating Evolution to Fight Disease.
S. M. Rosenberg and C. Queitsch (2014)
Science 343, 1088-1089
   Abstract »    Full Text »    PDF »
Cancer as a metabolic disease: implications for novel therapeutics.
T. N. Seyfried, R. E. Flores, A. M. Poff, and D. P. D'Agostino (2014)
Carcinogenesis 35, 515-527
   Abstract »    Full Text »    PDF »
PortEco: a resource for exploring bacterial biology through high-throughput data and analysis tools.
J. C. Hu, G. Sherlock, D. A. Siegele, S. A. Aleksander, C. A. Ball, J. Demeter, S. Gouni, T. A. Holland, P. D. Karp, J. E. Lewis, et al. (2014)
Nucleic Acids Res. 42, D677-D684
   Abstract »    Full Text »    PDF »
Hypermutability and error catastrophe due to defects in ribonucleotide reductase.
D. Ahluwalia and R. M. Schaaper (2013)
PNAS 110, 18596-18601
   Abstract »    Full Text »    PDF »
Structural insight into LexA-RecA* interaction.
L. Kovacic, N. Paulic, A. Leonardi, V. Hodnik, G. Anderluh, Z. Podlesek, D. Zgur-Bertok, I. Krizaj, and M. Butala (2013)
Nucleic Acids Res. 41, 9901-9910
   Abstract »    Full Text »    PDF »
Engineered proteins detect spontaneous DNA breakage in human and bacterial cells.
C. Shee, B. D. Cox, F. Gu, E. M. Luengas, M. C. Joshi, L.-Y. Chiu, D. Magnan, J. A. Halliday, R. L. Frisch, J. L. Gibson, et al. (2013)
eLife Sci 2, e01222
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882