TY - JOUR
T1 - Identity and function of a large gene network underlying mutagenic repair of DNA breaks
AU - Al Mamun, Abu Amar M.
AU - Lombardo, Mary Jane
AU - Shee, Chandan
AU - Lisewski, Andreas M.
AU - Gonzalez, Caleb
AU - Lin, Dongxu
AU - Nehring, Ralf B.
AU - Saint-Ruf, Claude
AU - Gibson, Janet L.
AU - Frisch, Ryan L.
AU - Lichtarge, Olivier
AU - Hastings, P. J.
AU - Rosenberg, Susan M.
PY - 2012/12/7
Y1 - 2012/12/7
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1226683
DO - 10.1126/science.1226683
M3 - Article
C2 - 23224554
AN - SCOPUS:84870665519
SN - 0036-8075
VL - 338
SP - 1344
EP - 1348
JO - Science
JF - Science
IS - 6112
ER -