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Titolo:
GENERATION AND ELIMINATION OF 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE 5'-TRIPHOSPHATE, A MUTAGENIC SUBSTRATE FOR DNA-SYNTHESIS, IN HUMAN-CELLS
Autore:
HAYAKAWA H; TAKETOMI A; SAKUMI K; KUWANO M; SEKIGUCHI M;
Indirizzi:
KYUSHU UNIV,FAC MED,DEPT BIOCHEM FUKUOKA 812 JAPAN KYUSHU UNIV,MED INST BIOREGULAT FUKUOKA 812 JAPAN
Titolo Testata:
Biochemistry
fascicolo: 1, volume: 34, anno: 1995,
pagine: 89 - 95
SICI:
0006-2960(1995)34:1<89:GAEO85>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESCHERICHIA-COLI; G.C->T.A TRANSVERSIONS; MUTY GENE; 8-HYDROXYGUANINE 7,8-DIHYDRO-8-OXOGUANINE; ENDONUCLEASE ACTIVITY; MUTATOR LOCUS; DAMAGED BASE; PROTEIN; GLYCOSYLASE; REPAIR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
H. Hayakawa et al., "GENERATION AND ELIMINATION OF 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE 5'-TRIPHOSPHATE, A MUTAGENIC SUBSTRATE FOR DNA-SYNTHESIS, IN HUMAN-CELLS", Biochemistry, 34(1), 1995, pp. 89-95

Abstract

8-Oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is apotent mutagenic substrate for DNA synthesis. The present study dealswith generation and degradation of 8-oxo-dGTP in the nucleotide pool of human cells. (1) 8-Oxo-dGTP can be generated not only by direct oxidation of dGTP but also by phosphorylation of 8-oxo-dGDP by nucleosidediphosphate kinase. (2) 8-Oxo-dGTP is rapidly degraded to 8-oxo-dGMP by cellular 8-oxo-dGTPase activity. 8-Oxo-dGMP thus produced cannot berephosphorylated; guanylate kinase, which phosphorylates both GMP anddGMP to the corresponding nucleoside diphosphates, is totally inactive for 8-oxo-dGMP. (3) 8-Oxo-dGMP is further degraded to 8-oxo-deoxyguanosine by a nucleotidase. The enzyme was partially purified from an extract of human Jurkat cells, and the mode of action was elucidated. 8-Oxo-dGMP is the most preferred substrate of the enzyme, and other nucleoside monophosphates are cleaved at significantly lower rates: K-m for 8-oxo-dGMP is 10 times lower than that for dGMP, the second best substrate for the enzyme. The enzyme appears to convert 8-oxo-dGMP, whichaccumulates in the cellular nucleotide pool, to a form readily excretable to the:cell exterior.

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Documento generato il 11/07/20 alle ore 03:40:45