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Titolo:
CLONING OF A YEAST 8-OXOGUANINE DNA GLYCOSYLASE REVEALS THE EXISTENCEOF A BASE-EXCISION DNA-REPAIR PROTEIN SUPERFAMILY
Autore:
NASH HM; BRUNER SD; SCHARER OD; KAWATE T; ADDONA TA; SPONNER E; LANE WS; VERDINE GL;
Indirizzi:
HARVARD UNIV,DEPT CHEM & CHEM BIOL,12 OXFORD ST CAMBRIDGE MA 02138 HARVARD UNIV,DEPT CHEM & CHEM BIOL CAMBRIDGE MA 02138 HARVARD MICROCHEM FACIL CAMBRIDGE MA 02138
Titolo Testata:
Current biology
fascicolo: 8, volume: 6, anno: 1996,
pagine: 968 - 980
SICI:
0960-9822(1996)6:8<968:COAY8D>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
CATALYTIC MECHANISM; FPG PROTEIN; 8-HYDROXYGUANINE 7,8-DIHYDRO-8-OXOGUANINE; SACCHAROMYCES-CEREVISIAE; MUTAGENIC SUBSTRATE; ENDONUCLEASE-III; N-GLYCOSYLASE; ENZYME; BINDING; INTERMEDIATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
H.M. Nash et al., "CLONING OF A YEAST 8-OXOGUANINE DNA GLYCOSYLASE REVEALS THE EXISTENCEOF A BASE-EXCISION DNA-REPAIR PROTEIN SUPERFAMILY", Current biology, 6(8), 1996, pp. 968-980

Abstract

Background: Reactive oxygen species, ionizing radiation, and other free radical generators initiate the conversion of guanine (G) residues in DNA to 8-oxoguanine ((O)G), which is highly mutagenic as it preferentially mispairs with adenine (A) during replication. Bacteria counterthis threat with a multicomponent system that excises the lesion, corrects (O)G:A mispairs and cleanses the nucleotide precursor pool of d(O)GTP. Although biochemical evidence has suggested the existence of base-excision DNA repair proteins specific for (O)G in eukaryotes, little is known about these proteins. Results: Using substrate-mimetic affinity chromatography followed by a mechanism-based covalent trapping procedure, we have isolated a base-excision DNA repair protein from Saccharomyces cerevisiae that processes (O)G opposite cytosine ((O)G:C) but acts only weakly on (O)G:A. A search of the yeast genome database using peptide sequences from the protein identified a gene, OGG1, encoding a predicted 43 kDa (376 amino acid) protein, identical to one identified independently by complementation cloning. Ogg1 has (O)G:C-specific base-excision DNA repair activity and also intrinsic beta-lyase activity, which proceeds through a Schiff base intermediate. Targeted disruption of the OGG1 gene in yeast revealed a second (O)G glycosylase/lyase protein, tentatively named OGG2, which differs from OGG1 in that it preferentially acts on (O)G:G. Conclusions: S. cerevisiae has two (O)G-specific glycosylase/lyases, which differ significantly in their preference for the base opposite the lesion. We suggest that one of these, Ogg1, is closely related in overall three-dimensional structure toEscherichia coli endonuclease III (endo III), a glycosylase/lyase that acts on fragmented and oxidatively damaged pyrimidines. We have recently shown that AlkA, a monofunctional DNA glycosylase that acts on alkylated bases, is structurally homologous to endo III. We have now identified a shared active site motif amongst these three proteins. Usingthis motif as a protein database searching tool, we find that it is present in a number of other base-excision DNA repair proteins that process diverse lesions. Thus, we propose the existence of a DNA glycosylase superfamily, members of which possess a common fold yet act upon remarkably diverse lesions, ranging from UV photoadducts to mismatches to alkylated or oxidized bases.

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Documento generato il 10/07/20 alle ore 15:35:15