Molecular Cloning and Functional Analysis of the MutY Homolog of
            <i>Deinococcus radiodurans</i>

Li, Xianghong; Lu, A-Lien

doi:10.1128/jb.183.21.6151-6158.2001

Cited by 15 publications

(9 citation statements)

References 59 publications

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“…MutY homologs are present in eukaryotes such as humans, mice, and yeast, as well as in the prokaryotes E. coli, B. subtilis, P. aeruginosa, D. radiodurans, N. meningitidis, and N. gonorrhoeae [17][18][19][20][21][22]. The functions and mechanisms of E. coli MutY have been well studied [13,14,23,25,26,[28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori

2007

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MutY is an adenine glycosylase that has the ability to efficiently remove adenines from adenine/7,8-dihydro-8-oxoguanine (8-oxo-G) or adenine/guanine mismatches, and plays an important role in oxidative DNA damage repair. The human gastric pathogen Helicobacter pylori has a homolog of the MutY enzyme. To investigate the physiological roles of MutY in H. pylori, we constructed and characterized a mutY mutant. H. pylori mutY mutants incubated at 5% O 2 have a 325 fold higher spontaneous mutation rate than its parent. The mutation rate is further increased by exposing the mutant to atmospheric levels of oxygen, an effect that is not seen in an E. coli mutY mutant. Most of the mutations that occurred in H. pylori mutY mutants, as examined by rpoB sequence changes that confer rifampicin resistance, are GC to TA transversions. The H. pylori enzyme has the ability to complement an E. coli mutY mutant, restoring its mutation frequency to the wild-type level. Pure H. pylori MutY has the ability to remove adenines from A/8-oxo-G mismatches, but strikingly no ability to cleave A/G mismatches. This is surprising because E. coli MutY can more rapidly turnover A/G than A/8-oxo-G. Thus, H. pylori MutY is an adenine glycosylase involved in the repair of oxidative DNA damage with a specificity for detecting 8-oxo-G. In addition, H. pylori mutY mutants are only 30% as efficient as wild-type in colonizing the stomach of mice, indicating that H. pylori MutY plays a significant role in oxidative DNA damage repair in vivo.

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Section: Introductionmentioning

confidence: 99%

Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori

2007

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“…D. radiodurans MutY (DR2285) is a monofunctional 8-oxoguanine glycosylase active on A/G, A/C, and A/GO mismatches, with a binding preference for A/GO mismatches and with kinetic parameters similar to those of E. coli MutY (356). D. radiodurans MutY complements the E. coli mutY mutant (356). In contrast to E. coli MutM, deinococcal MutM (DR0493) is able to excise GO from A/GO mismatches (546).…”

Section: Resistance Of D Radiodurans To Base-damaging Chemicalsmentioning

confidence: 99%

“…However, if this does not occur and replication takes place, the DNA glycosylase MutY intercepts the resultant GO/A mismatches and removes the inappropriate adenine, leaving AP/GO, which is a substrate for MutM (622). D. radiodurans MutY (DR2285) is a monofunctional 8-oxoguanine glycosylase active on A/G, A/C, and A/GO mismatches, with a binding preference for A/GO mismatches and with kinetic parameters similar to those of E. coli MutY (356). D. radiodurans MutY complements the E. coli mutY mutant (356).…”

Section: Resistance Of D Radiodurans To Base-damaging Chemicalsmentioning

confidence: 99%

Oxidative Stress Resistance inDeinococcus radiodurans

Slade

Radman

2011

Microbiol Mol Biol Rev

660

639

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SUMMARY Deinococcus radiodurans is a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience of D. radiodurans to oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems. D. radiodurans assets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such as D. radiodurans have substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook on D. radiodurans strategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection in D. radiodurans is therefore of considerable potential interest for medicine and public health.

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“…An evolutionary analysis of the HhH superfamily of DNA repair glycosylases performed by Denver et al shows that MutY is present in most bacteria, many eukaryotes, and nearly 50% of the archaea investigated (9). The crystal structure of E. coli MutY has been solved (15,19), and the gene has been cloned and characterized in a range of species, including mammals (23,24,28,43). However, none of these species are directly comparable with MC.…”

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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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Molecular Cloning and Functional Analysis of the MutY Homolog of Deinococcus radiodurans

Abstract: The mutY homolog gene (mutY Dr

Cited by 15 publications

References 59 publications

Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori

Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori

Oxidative Stress Resistance inDeinococcus radiodurans

Antimutator Role of DNA Glycosylase MutY in Pathogenic Neisseria Species

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