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

被引：174

作者：

Al Mamun, Abu Amar M. ^{[1
]}

Lombardo, Mary-Jane ^{[1
]}

Shee, Chandan ^{[1
]}

Lisewski, Andreas M. ^{[1
]}

Gonzalez, Caleb ^{[1
]}

Lin, Dongxu ^{[1
]}

Nehring, Ralf B. ^{[1
]}

Saint-Ruf, Claude ^{[2
]}

Gibson, Janet L. ^{[1
]}

Frisch, Ryan L. ^{[1
]}

Lichtarge, Olivier ^{[1
,3
]}

Hastings, P. J. ^{[1
]}

Rosenberg, Susan M. ^{[1
,3
,4
,5
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Univ Paris, INSERM, U1001, F-75730 Paris 15, France

[3] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

[5] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

来源：

SCIENCE | 2012年 / 338卷 / 6112期

基金：

美国国家科学基金会;

关键词：

STRESS-INDUCED MUTATION; ESCHERICHIA-COLI; SIGMA-FACTOR; EXPRESSION; DATABASE; SWITCH;

D O I：

10.1126/science.1226683

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1344 / 1348

页数：5

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