Negative regulation of mutS and mutH repair gene expression by the Hfq and RpoS global regulators of Escherichia coli K-12

Tsui, Ho‐Ching Tiffany; Feng, Gang; Winkler, Malcolm E.

doi:10.1128/jb.179.23.7476-7487.1997

Cited by 185 publications

(207 citation statements)

References 76 publications

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“…Our results also have a forensic implication. Because the activity of the MMR varies by growth phase and is influenced by environmental conditions (19,20), an organism's mutational spectrum might be a fingerprint of its recent history.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the presence or absence of various DNA repair pathways can be quite sporadic among microbial species (16)(17)(18). In addition, MMR proteins are subject to regulation (19,20), and thus the activity of MMR is responsive to both intrinsic and extrinsic factors. For these reasons, we have included in this report the results of an MA experiment with an isogenic MMR-defective strain.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Lee¹,

Popodi

Tang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

640

131

859

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Knowledge of the rate and nature of spontaneous mutation is fundamental to understanding evolutionary and molecular processes. In this report, we analyze spontaneous mutations accumulated over thousands of generations by wild-type Escherichia coli and a derivative defective in mismatch repair (MMR), the primary pathway for correcting replication errors. The major conclusions are (i) the mutation rate of a wild-type E. coli strain is ∼1 × 10 −3 per genome per generation; (ii) mutations in the wild-type strain have the expected mutational bias for G:C > A:T mutations, but the bias changes to A:T > G:C mutations in the absence of MMR; (iii) during replication, A:T > G:C transitions preferentially occur with A templating the lagging strand and T templating the leading strand, whereas G:C > A:T transitions preferentially occur with C templating the lagging strand and G templating the leading strand; (iv) there is a strong bias for transition mutations to occur at 5′ApC3′/3′TpG5′ sites (where bases 5′A and 3′T are mutated) and, to a lesser extent, at 5′GpC3′/3′CpG5′ sites (where bases 5′G and 3′C are mutated); (v) although the rate of small (≤4 nt) insertions and deletions is high at repeat sequences, these events occur at only 1/10th the genomic rate of base-pair substitutions. MMR activity is genetically regulated, and bacteria isolated from nature often lack MMR capacity, suggesting that modulation of MMR can be adaptive. Thus, comparing results from the wild-type and MMR-defective strains may lead to a deeper understanding of factors that determine mutation rates and spectra, how these factors may differ among organisms, and how they may be shaped by environmental conditions. evolution | mutation accumulation | neutral mutation | mutational hotspots | indels M utations are the source of variation upon which natural selection acts; thus, a complete understanding of evolutionary processes must include an accurate assessment of mutation rates and of the molecular spectrum of mutational events. In addition, we need to know whether, and how, intrinsic and extrinsic factors influence mutational processes. This understanding must be founded on baseline parameters established by analyzing mutations that accumulate in a neutral fashion, unbiased by selective pressures. Much of our knowledge of spontaneous mutation is based on mutations that occur in nonessential reporter genes during short-term laboratory culture of microorganisms (1). An alternative approach is to compare presumably neutral mutations that have accumulated over evolutionary time periods in diverged species (2). Both methods have substantial uncertainties. The experimental approach may use reporter loci that are not representative of the whole genome and necessarily incorporates assumptions about the expression and neutrality of the mutant phenotypes. The historical approach relies on estimated divergence times and the absence of selective pressure on synonymous sequence changes. High-throughput whole-genome sequencing allows some of these limitations to be...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Lee¹,

Popodi

Tang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

640

131

859

View full text Add to dashboard Cite

show abstract

“…Mismatch repair also inhibits recombination between diverged DNA, insuring that species integrity is maintained (reviewed in [20]). In E. coli key components of mismatch repair, particularly MutS (but not MutL), are down regulated in stationary-phase cells under control of RpoS [21,22]. Although mismatch repair is still active during starvation [23], certain cells in a starving population may have such low levels of the mismatch repair proteins that DNA polymerase errors are preserved.…”

Section: The General Stress Responsementioning

confidence: 99%

“…In addition, Pol IV is positively regulated by the general-stress sigma factor RpoS [18], and is expressed in starving cells [18,19]. Key components of mismatch repair are down regulated under control of RpoS [22]. Although mismatch repair is active during lactose selection [40], the fact that mismatch repair proteins are in low supply may mean that in some cells the pathway is saturated, or some components are not present (as suggested by Ninio [67]), giving rise to the hypermutator population.…”

Section: Summary and Significancementioning

confidence: 99%

Stress responses and genetic variation in bacteria

Foster

2005

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

177

106

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Under stressful conditions mechanisms that increase genetic variation can bestow a selective advantage. Bacteria have several stress responses that provide ways in which mutation rates can be increased. These include the SOS response, the general stress response, the heat-shock response, and the stringent response, all of which impact the regulation of error-prone polymerases. Adaptive mutation appears to be process by which cells can respond to selective pressure specifically by producing mutations. In Escherichia coli strain FC40 adaptive mutation involves the following inducible components: (i) a recombination pathway that generates mutations; (ii) a DNA polymerase that synthesizes error-containing DNA; and (iii) stress responses that regulate cellular processes. In addition, a subpopulation of cells enters into a state of hypermutation, giving rise to about 10% of the single mutants and virtually all of the mutants with multiple mutations. These bacterial responses have implications for the development of cancer and other genetic disorders in higher organisms.

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“…The rssB::tetA (10) and iraD::tetA alleles (S. Gottesman, National Institutes of Health) were introduced by P1 transduction into MG1655, generating STL11118 and STL11119, respectively. STL7291 (rpoS::Tn10) was derived by Winkler and coworkers (36), published previously as TX3740. The hsdR⌬::FRT kan allele from the Mori collection (37) was transduced into MG1655, generating STL11795, and was used as a linked marker with which to move iraD⌬::tetA in strains already resistant to tetracycline.…”

Section: Methodsmentioning

confidence: 99%

A DNA damage response in Escherichia coli involving the alternative sigma factor, RpoS

Merrikh

Ferrazzoli

Bougdour

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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We isolated an Escherichia coli mutant in the iraD gene, sensitive to various forms of DNA damage. Our data are consistent with the function of IraD to promote accumulation of the alternative transcription sigma factor, RpoS, by binding to the adaptor RssB protein that targets RpoS for degradation. Our results demonstrate the physiological importance of this mode of regulation for DNA damage tolerance. Although RpoS is best known for its regulation of genes induced in stationary phase, our work underscores the importance of the RpoS regulon in a DNA damage response in actively growing cells. We show that iraD transcription is induced by DNA damage by a mechanism independent of the SOS response. The IraD and SOS regulatory pathways appear to act synergistically to ensure survival of cells faced with oxidative or DNA damaging stress during cellular growth.oxidative stress ͉ posttranslational regulation ͉ replication stress ͉ SOS response ͉ DNA repair T hroughout its life cycle, Escherichia coli is faced with different environmental challenges and regulates gene expression accordingly. One way is by changes in the promoter recognition of RNA polymerase via different situation-specific factors (1). In E. coli, the major alternative sigma factor is S (RpoS), which is required for expression of specific genes on entry to stationary phase or as a response to stress (2-4). Although the RpoS dependence of many of these responses and the regulation of RpoS itself have been well studied, the relevance of this to DNA repair has not been a major focus.To find genes important in DNA damage responses, we performed a random Tn5 transposon insertion mutant screen, assaying sensitivity to, among other agents, phleomycin and azidothymidine (AZT). Phleomycin induces random single-or double-strand breaks in the backbone of DNA (5), whereas AZT blocks DNA synthesis, leading to single-strand gaps in the replication fork (6). One insertion mutant in iraD (previously an unknown gene, yjiD) was hypersensitive to phleomycin and AZT.Recent work from Gottesman and coworkers (7) implicated IraD in posttranslational regulation of RpoS. The RssB adaptor protein targets RpoS to ClpXP for degradation during logarithmic growth, keeping RpoS protein levels low in the absence of stress (8-12). IraD was identified in a high-copy plasmid screen for genes promoting accumulation of an RpoS-LacZ fusion protein. The IraD gene product acts as an antiadaptor protein via direct binding and inhibition of the ability of RssB to target RpoS for proteolysis by ClpXP in vitro (7).In the work presented here, we demonstrate that IraD is required for survival to DNA damage, providing evidence of the physiological importance of IraD in particular and the antiadaptor mechanism in general. The data presented suggest that IraD acts as an antagonist of RssB, regulating RpoS levels and stabilization, not only after DNA damage but constitutively. Our results establish the importance of RpoS stabilization in proliferating bacterial cells in which replication has been direc...

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Negative regulation of mutS and mutH repair gene expression by the Hfq and RpoS global regulators of Escherichia coli K-12

Cited by 185 publications

References 76 publications

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

Stress responses and genetic variation in bacteria

A DNA damage response in Escherichia coli involving the alternative sigma factor, RpoS

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