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Titolo:
OPPOSITE BASE-DEPENDENT REACTIONS OF A HUMAN BASE EXCISION-REPAIR ENZYME ON DNA CONTAINING 7,8-DIHYDRO-8-OXOGUANINE AND ABASIC SITES
Autore:
BJORAS M; LUNA L; JOHNSON B; HOFF E; HAUG T; ROGNES T; SEEBERG E;
Indirizzi:
UNIV OSLO,NATL HOSP,INST MED MICROBIOL,DEPT BIOL MOL N-0027 OSLO NORWAY UNIV OSLO,NATL HOSP,INST MED MICROBIOL,DEPT BIOL MOL N-0027 OSLO NORWAY NATL HOSP NORWAY,CTR OCCUPAT & ENVIRONM MED N-0027 OSLO NORWAY
Titolo Testata:
EMBO journal
fascicolo: 20, volume: 16, anno: 1997,
pagine: 6314 - 6322
SICI:
0261-4189(1997)16:20<6314:OBROAH>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
OPEN RING 7-METHYLGUANINE; ESCHERICHIA-COLI; ENDONUCLEASE-III; 8-HYDROXYGUANINE 7,8-DIHYDRO-8-OXOGUANINE; SACCHAROMYCES-CEREVISIAE; SUBSTRATE-SPECIFICITY; MUTAGENIC SUBSTRATE; IONIZING-RADIATION; OXIDATIVE DAMAGE; GLYCOSYLASE;
Keywords:
AP-LYASE; BASE EXCISION; DNA GLYCOSYLASE; DNA REPAIR; 8-OXOGUANINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
M. Bjoras et al., "OPPOSITE BASE-DEPENDENT REACTIONS OF A HUMAN BASE EXCISION-REPAIR ENZYME ON DNA CONTAINING 7,8-DIHYDRO-8-OXOGUANINE AND ABASIC SITES", EMBO journal, 16(20), 1997, pp. 6314-6322

Abstract

The guanine modifications 7,8-dihydro-8-oxoguanine (8-axoG) is a potent premutagenic lesion formed spontaneously at high frequencies in thegenomes of aerobic organisms. We have characterized a human DNA repair glycosylase for 8-oxoG removal, hOGH1 (human yeast OGG1 homologue), by molecular cloning and functional analysis;Expression of the human cDNA in a repair deficient mutator strain of Escherichia coli (fpg mutY) suppressed the spontaneous mutation frequency to almost normal levels, The hOGH1 enzyme was localized to the nucleus in cells transfected by constructs of hOGH1 fused to green fluorescent protein, Enzyme purification yielded a protein of 38 kDa removing both formamidopyrimidines and 8-oxoG from DNA, The enzymatic activities of hOGH1 was analysed on DNA containing single residues of 8-oxoG or abasic sites opposite each of the four normal bases in DNA, Excision of 8-oxoG opposite C wasthe most efficient and was followed by strand cleavage via beta-elimination. However, significant removal of 8-oxoG from mispairs (8-oxoG: T >G >A) was also demonstrated, but essentially without am associated strand cleavage reaction. Assays with abasic site DIVA showed that strand cleavage was indeed dependent on the presence of C in the oppositestrand, irrespective of the prior removal of an 8-oxoG residue, It thus appears that strand incisions are made only if repair completion results in correct base insertion, whereas excision from mispairs preserves strand continuity and hence allows for error-free correction by a postreplicational repair mechanism.

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Documento generato il 07/07/20 alle ore 17:40:46