Translesion DNA Synthesis and Mutagenesis in Prokaryotes

Fuchs, Robert P. P.; Fujii, Shingo

doi:10.1101/cshperspect.a012682

Cited by 116 publications

(124 citation statements)

References 128 publications

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“…From a practical viewpoint, recent findings also uncover clinical significance of the SOS pathway in the response to diverse antibiotics and also in the spread of virulence and drug-resistance genes. The reader is referred to several excellent recent reviews on various aspects of the SOS response (Michel 2005;Aertsen and Michiels 2006;Kelley 2006;Erill et al 2007;Butala et al 2009;Ayora et al 2011) and to Fuchs and Fujii (2013) on bacterial translesion synthesis (TLS) polymerases for a discussion of this aspect of the SOS response.…”

Section: The Sos Responsementioning

confidence: 99%

DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks

Kreuzer

2013

Cold Spring Harbor Perspectives in Biology

205

185

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Recent advances in the area of bacterial DNA damage responses are reviewed here. The SOS pathway is still the major paradigm of bacterial DNA damage response, and recent studies have clarified the mechanisms of SOS induction and key physiological roles of SOS including a very major role in genetic exchange and variation. When considering diverse bacteria, it is clear that SOS is not a uniform pathway with one purpose, but rather a platform that has evolved for differing functions in different bacteria. Relating in part to the SOS response, the field has uncovered multiple apparent cell-cycle checkpoints that assist cell survival after DNA damage and remarkable pathways that induce programmed cell death in bacteria. Bacterial DNA damage responses are also much broader than SOS, and several important examples of LexA-independent regulation will be reviewed. Finally, some recent advances that relate to the replication and repair of damaged DNA will be summarized. Since the publication of DNA Repair and Mutagenesis in 2006 (Friedberg et al. 2006), our understanding of bacterial DNA damage responses has progressed significantly. Some studies have refined known pathways and filled in important details, whereas other studies have uncovered surprising new pathways such as bacterial programmed cell death and a form of replicative repair that reconstitutes severely shattered genomes. This review will focus on these recent advances, with only limited discussion and citation to work that precedes the 2006 tome. THE SOS RESPONSEAs scientists have studied the SOS response in Escherichia coli and other bacteria over the last decade, our understanding of SOS has changed in unexpected ways and the pathway has been found integrated in diverse cellular processes. Our understanding of the mechanism of SOS induction has also advanced in recent years, including a view of induction at the single-cell level. A surprising finding is that the functions of the SOS pathway are not uniform between bacterial species, and so the view of SOS as

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Section: The Sos Responsementioning

confidence: 99%

DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks

Kreuzer

2013

Cold Spring Harbor Perspectives in Biology

205

185

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“…Two of these, DNA polymerase V (Pol V, encoded by the umuDC genes) and DNA polymerase IV (Pol IV, encoded by the dinB gene), are intrinsically error prone, whereas the third, DNA polymerase II (Pol II, encoded by the polB gene), is accurate (reviewed in ref. 19). Although there are few (≤15) molecules of Pol V in uninduced cells, transient induction of Pol V during normal growth could be mutagenic (20).…”

Section: Significancementioning

confidence: 99%

Determinants of spontaneous mutation in the bacteriumEscherichia colias revealed by whole-genome sequencing

Foster

Lee

Popodi

et al. 2015

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

150

205

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A complete understanding of evolutionary processes requires that factors determining spontaneous mutation rates and spectra be identified and characterized. Using mutation accumulation followed by whole-genome sequencing, we found that the mutation rates of three widely diverged commensal Escherichia coli strains differ only by about 50%, suggesting that a rate of 1-2 × 10 −3 mutations per generation per genome is common for this bacterium. Four major forces are postulated to contribute to spontaneous mutations: intrinsic DNA polymerase errors, endogenously induced DNA damage, DNA damage caused by exogenous agents, and the activities of error-prone polymerases. To determine the relative importance of these factors, we studied 11 strains, each defective for a major DNA repair pathway. The striking result was that only loss of the ability to prevent or repair oxidative DNA damage significantly impacted mutation rates or spectra. These results suggest that, with the exception of oxidative damage, endogenously induced DNA damage does not perturb the overall accuracy of DNA replication in normally growing cells and that repair pathways may exist primarily to defend against exogenously induced DNA damage. The thousands of mutations caused by oxidative damage recovered across the entire genome revealed strong local-sequence biases of these mutations. Specifically, we found that the identity of the 3′ base can affect the mutability of a purine by oxidative damage by as much as eightfold.A complete understanding of the evolution and stability of the genome requires that the determinants of spontaneous mutation be identified and characterized. Among the variety of mistakes that can occur during DNA transactions, four sources of sequence variation appear to dominate in prokaryotes: intrinsic DNA polymerase errors, endogenously induced DNA damage, DNA damage induced by exogenous agents, and the activities of error-prone polymerases. This conclusion is based on changes in the rates and spectra of mutations that occur when genes affecting these processes are deleted or amplified. In particular, loss of a DNA repair pathway often gives a mutator phenotype, indicating that the pathway of interest exerts an important limitation on spontaneous mutation (1). However, investigations of the mutagenic impact of various DNA repair pathways have relied almost exclusively on reporter genes, leaving open the possibility that the results are biased by the particular features of the selected loci. This concern can be avoided by allowing mutations to accumulate nonselectively in DNA repair-defective strains and identifying the resulting sequence changes by whole-genome sequencing (WGS). Although this approach may miss rare but interesting mutational processes, it can reveal the overall threats to genomic stability and identify features, such as local sequence context, that influence mutational frequencies. Surprisingly, this technique has been used with the eukaryote Caenorhabditis elegans (2) but has not been extensively applied to prokary...

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“…It is well known that Y-family polymerases facilitate replication progression past bulky lesions on the DNA after damage (16)(17)(18)(19)(20). The lesion bypass activity of these polymerases is error-prone, leading to increased mutagenesis (21)(22)(23).…”

mentioning

confidence: 99%

An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis

Million-Weaver¹,

Samadpour²,

Moreno-Habel³

et al. 2015

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

128

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We previously reported that lagging-strand genes accumulate mutations faster than those encoded on the leading strand in Bacillus subtilis. Although we proposed that orientation-specific encounters between replication and transcription underlie this phenomenon, the mechanism leading to the increased mutagenesis of lagging-strand genes remained unknown. Here, we report that the transcription-dependent and orientation-specific differences in mutation rates of genes require the B. subtilis Y-family polymerase, PolY1 (yqjH). We find that without PolY1, association of the replicative helicase, DnaC, and the recombination protein, RecA, with lagging-strand genes increases in a transcription-dependent manner. These data suggest that PolY1 promotes efficient replisome progression through lagging-strand genes, thereby reducing potentially detrimental breaks and single-stranded DNA at these loci. Y-family polymerases can alleviate potential obstacles to replisome progression by facilitating DNA lesion bypass, extension of D-loops, or excision repair. We find that the nucleotide excision repair (NER) proteins UvrA, UvrB, and UvrC, but not RecA, are required for transcription-dependent asymmetry in mutation rates of genes in the two orientations. Furthermore, we find that the transcription-coupling repair factor Mfd functions in the same pathway as PolY1 and is also required for increased mutagenesis of laggingstrand genes. Experimental and SNP analyses of B. subtilis genomes show mutational footprints consistent with these findings. We propose that the interplay between replication and transcription increases lesion susceptibility of, specifically, lagging-strand genes, activating an Mfd-dependent error-prone NER mechanism. We propose that this process, at least partially, underlies the accelerated evolution of lagging-strand genes.replication conflicts | transcription orientation | Y-family polymerases | excision repair | TCR

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Translesion DNA Synthesis and Mutagenesis in Prokaryotes

Cited by 116 publications

References 128 publications

DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks

DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks

Determinants of spontaneous mutation in the bacteriumEscherichia colias revealed by whole-genome sequencing

An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis

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