Competition between MutY and Mismatch Repair at A · C Mispairs In Vivo

Kim, Mandy; Huang, Tiffany; Miller, Jeffrey H

doi:10.1128/jb.185.15.4626-4629.2003

Cited by 36 publications

(38 citation statements)

References 23 publications

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“…The results are reproducible and are statistically significant (P ϭ 0.008). These results differ from the findings of Kim et al (27), who mentioned that the mutation frequencies of mutS and mutS mutY were similar. No data, however, were shown to support those findings of Kim et al (27).…”

Section: Resultscontrasting

confidence: 57%

“…E. coli chromosomal DNA was isolated using a genomic DNA purification kit (Gentra System, Minneapolis, MN). The main group of mutations (cluster II) of the rpoB gene was PCR amplified using Chang440 and Chang441 primers (see Table S1 in the supplemental material) as described previously (27). The PCR product was purified with the QIAquick PCR purification kit (QIAGEN, Valencia, CA) and sequenced directly with Chang442 primer.…”

Section: Methodsmentioning

confidence: 99%

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Physical and Functional Interactions between Escherichia coli MutY Glycosylase and Mismatch Repair Protein MutS

Bai

2007

J Bacteriol

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Section: Resultscontrasting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Physical and Functional Interactions between Escherichia coli MutY Glycosylase and Mismatch Repair Protein MutS

Bai

2007

J Bacteriol

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“…Whether error correction by epsilon is biased has been debated for years, but a recent study (56) showed a bias toward correcting G:C > A:T mutations that would account for our results. Another candidate is MutY, which can remove an A mispaired with C, preventing G:C > A:T mutations if C is the template (and promoting A:T > G:C mutations if A is the template) (57). Future MA studies will reveal if these enzymes contribute to mutational specificity in the absence of MMR.…”

Section: Discussionmentioning

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

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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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“…Moreover, Richardson et al (40,41) found that mutS and mutL deficiencies only partly explain the high mutation rate of some MC isolates. As MutY represents a mismatch excision function in removing adenine opposite guanine (32) or cytosine (51) and previously has been shown to overlap with E. coli MMR in vivo (22), a coupling between MC BER and MMR could result in a hypermutator phenotype of mutY mutant strains.…”

Section: Discussionmentioning

confidence: 99%

Antimutator Role of DNA Glycosylase MutY in Pathogenic Neisseria Species

et al. 2005

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Genome alterations due to horizontal gene transfer and stress constantly generate strain on the gene pool of Neisseria meningitidis, the causative agent of meningococcal (MC) disease. The DNA glycosylase MutY of the base excision repair pathway is involved in the protection against oxidative stress. MC MutY expressed in Escherichia coli exhibited base excision activity towards DNA substrates containing A:7,8-dihydro-8-oxo-2-deoxyguanosine and A:C mismatches. Expression in E. coli fully suppressed the elevated spontaneous mutation rate found in the E. coli mutY mutant. An assessment of MutY activity in lysates of neisserial wild-type and mutY mutant strains showed that both MC and gonococcal (GC) MutY is expressed and active in vivo. Strikingly, MC and GC mutY mutants exhibited 60-to 140-fold and 20-fold increases in mutation rates, respectively, compared to the wild-type strains. Moreover, the differences in transitions and transversions in rpoB conferring rifampin resistance observed with the wild type and mutants demonstrated that the neisserial MutY enzyme works in preventing GC3AT transversions. These findings are important in the context of models linking mutator phenotypes of disease isolates to microbial fitness.Infections caused by Neisseria meningitidis (the meningococcus; MC) and Neisseria gonorrhoeae (the gonococcus; GC), pathogenic members of the genus Neisseria, are associated with significant morbidity and mortality in their exclusive human host. MC and GC residing on mucosal surfaces are exposed to DNA-damaging agents from a potent immune system and also suffer genotoxic stress from endogenous sources, predisposing factors for mutations (29,36). Mutator strains exhibit an increased spontaneous mutation rate compared to those commonly found in the corresponding wild-type species (17). Such a phenotype is often caused by heritable changes in components of the methyl-directed mismatch repair (MMR) pathway engaged in postreplication repair. However, Richardson et al. (41) demonstrated that only 39% of MC strains exhibiting elevated spontaneous mutation rates could be fully or partially complemented with wild-type mutS or mutL alleles and thus directly linked to defects in the MMR system. Conflicting evidence exists on the association of Dam methylase variants causing hypermutable neisserial strains with enhanced phasevariable capsule switching (4, 21, 40). Clearly, mechanisms other than MMR are implicated in MC mutator phenotypes. Associations between hypermutation and defects in MMR have not yet been reported in the close relative GC.One of the most frequent forms of oxidative DNA damage is the oxidation product of guanine, 7,8-dihydro-8-oxo-2Ј-deoxyguanosine (8oxoG) (8). The base excision repair (BER) pathway is probably the cell's major line of defense against the deleterious effects of such DNA damage (45). BER involves the release of modified base residues from DNA by DNA glycosylases that leave abasic (AP) sites in the DNA. The AP site may be further cleaved by an AP-lyase activity inherent ...

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Competition between MutY and Mismatch Repair at A · C Mispairs In Vivo

Cited by 36 publications

References 23 publications

Physical and Functional Interactions between Escherichia coli MutY Glycosylase and Mismatch Repair Protein MutS

Physical and Functional Interactions between Escherichia coli MutY Glycosylase and Mismatch Repair Protein MutS

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

Antimutator Role of DNA Glycosylase MutY in Pathogenic Neisseria Species

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