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Titolo:
Fission yeast (Schizosaccharomyces pombe) cells defective in the MutY-homologous glycosylase activity have a mutator phenotype and are sensitive to hydrogen peroxide
Autore:
Chang, DY; Gu, Y; Lu, AL;
Indirizzi:
Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 & Mol Biol, Baltimore, MD 21201 USA
Titolo Testata:
MOLECULAR GENETICS AND GENOMICS
fascicolo: 2, volume: 266, anno: 2001,
pagine: 336 - 342
SICI:
1617-4615(200110)266:2<336:FY(PCD>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESCHERICHIA-COLI MUTY; C-TERMINAL DOMAIN; ADENINE-DNA GLYCOSYLASE; MISMATCH REPAIR; 8-HYDROXYGUANINE 7,8-DIHYDRO-8-OXOGUANINE; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL EXPRESSION; SUBSTRATE-SPECIFICITY; MUTAGENIC SUBSTRATE; CATALYTIC DOMAIN;
Keywords:
fission yeast; MutY homolog (MYH); DNA repair; mutator; oxidative DNA damage;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Lu, AL Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 Biol, Baltimore, MD 21201 USA
Citazione:
D.Y. Chang et al., "Fission yeast (Schizosaccharomyces pombe) cells defective in the MutY-homologous glycosylase activity have a mutator phenotype and are sensitive to hydrogen peroxide", MOL GENET G, 266(2), 2001, pp. 336-342

Abstract

The modified base 7,8-dihydro-8-oxo-guanine (8-oxoG) is one of the most stable deleterious products of oxidative DNA damage because it mispairs with adenine during DNA replication. In the fission yeast Schizosaccharomyces pombe, the MutY homolog (SpMYH) is responsible for removing misincorporated adenines from A/8-oxoG or A/G mismatches and thus preventing G:C to T:A mutations. In order to study the functional role of SpMYH, an SpMYH knockout strain was constructed. The SpMYH knockout strain, which does not express SpMYH and has no A/8-oxoG glycosylase activity, displays a 36-fold higher frequency of spontaneous mutations than the wild type strain. Disruption of SpMYH causes increased sensitivity to H2O2 but not to UV-irradiation. Expression of SpMYH in the mutant cells restores the adenine glycosylase activity, reduces the mutation frequency, and elevates the resistance to H2O2. Asp172of SpMYH is conserved in a helix-hairpin-helix superfamily of glycosylases. The SpMYH Delta strain expressing D172N SpMYH retained the mutator phenotype. Moreover, when D172N mutant SpMYH was expressed in the wild-type cells, the mutation frequency observed was even higher than that of the parentalstrains. Thus, a mutant SpMYH that retains substrate-binding activity but is defective in glycosylase activity exhibits a dominant negative effect. This is the first demonstration that a MutY homolog plays an important role in protecting cells against oxidative DNA damage in eukaryotes.

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Documento generato il 16/07/20 alle ore 16:42:03