2012
DOI: 10.1126/science.1226683
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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 net… Show more

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Cited by 207 publications
(301 citation statements)
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“…However, the operation of additional mechanisms that contribute to hypermutability and poor growth cannot be excluded and should be considered. In particular, it is likely that the hypermutators accumulate mutated (misfolded) proteins that can trigger defined stress responses, contributing to the poor growth and mutability (37,39,40,42,44). In contrast to the high concentrations of the cellular rNTPs, which are generally in the millimolar range, those of the dNTPs are in the low-to mid-micromolar range (45)(46)(47)(48)(49).…”
Section: Discussionmentioning
confidence: 99%
“…However, the operation of additional mechanisms that contribute to hypermutability and poor growth cannot be excluded and should be considered. In particular, it is likely that the hypermutators accumulate mutated (misfolded) proteins that can trigger defined stress responses, contributing to the poor growth and mutability (37,39,40,42,44). In contrast to the high concentrations of the cellular rNTPs, which are generally in the millimolar range, those of the dNTPs are in the low-to mid-micromolar range (45)(46)(47)(48)(49).…”
Section: Discussionmentioning
confidence: 99%
“…16 Mdh is also believed to play a role in promoting the stressinduced mutagenesis response of E. coli. 17 SucD is the a subunit of succinyl-CoA synthetase, which catalyzes the only substrate-level phosphorylation reaction in the TCA cycle. 18 Some components of the electron transport chain, including NADH dehydrogenase I subunits NuoB and NuoE and succinate dehydrogenase subunit SdhA, presented an increased expression level under 3HP stress.…”
Section: Proteins Involved In Energy Metabolismmentioning
confidence: 99%
“…Thus, there are three main hubs of stress-response regulation of MBR (Al Mamun et al 2012;Rosenberg et al 2012): (1) formation of a DSB, which RpoE promotes , and its repair, (2) SOS induction, which upregulates DinB about 10-fold transcriptionally , and (3) activation of the RpoS general stress response, which allows DinB and other low-fidelity DNA polymerases to participate in DSB repair by as yet unknown means (Ponder et al 2005;Frisch et al 2010;Shee et al 2011;Rosenberg et al 2012). Previous studies showed that the NAP HU was required for MBR, possibly by promoting HR (Williams and Foster 2007).…”
mentioning
confidence: 99%