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Titolo:
IN SEARCH OF A MUTATIONAL HOTSPOT
Autore:
HATAHET Z; ZHOU MX; REHAKRANTZ LJ; MORRICAL SW; WALLACE SS;
Indirizzi:
UNIV VERMONT,DEPT MICROBIOL & MOL GENET BURLINGTON VT 05405 UNIV VERMONT,DEPT MICROBIOL & MOL GENET BURLINGTON VT 05405 UNIV VERMONT,MARKEY CTR MOL GENET BURLINGTON VT 05405 UNIV VERMONT,DEPT BIOCHEM BURLINGTON VT 05405 UNIV ALBERTA,DEPT SCI BIOL EDMONTON AB T6G 2E9 CANADA
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 15, volume: 95, anno: 1998,
pagine: 8556 - 8561
SICI:
0027-8424(1998)95:15<8556:ISOAMH>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
FORMAMIDOPYRIMIDINE-DNA GLYCOSYLASE; HA-RAS GENE; ESCHERICHIA-COLI; 8-HYDROXYGUANINE 7,8-DIHYDRO-8-OXOGUANINE; SUBSTRATE-SPECIFICITY; SEQUENCE CONTEXT; FPG PROTEIN; FRAGMENTATION PRODUCTS; OXIDATIVE DAMAGE; ENDONUCLEASE-III;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
Z. Hatahet et al., "IN SEARCH OF A MUTATIONAL HOTSPOT", Proceedings of the National Academy of Sciences of the United Statesof America, 95(15), 1998, pp. 8556-8561

Abstract

In vitro selection was used to define sequence contexts that significantly enhanced the mutagenic potential of 7,8-dihydro-8-oxoguanine (8-oxoG). Contexts that simultaneously reduced the efficiency of 8-oxoG cleavage by formamidopyrimidine DNA N-glycosylase and increased the efficiency of misincorporating A opposite the lesion by DNA polymerase were isolated from a pool of 4(8) random octanucleotide sequences. Kinetic analysis showed that the combined effects of poor repair and high miscoding resulted in 10(2)- to 10(3)-fold increase in the mutagenic potential of 8-oxoG. Furthermore, the isolated sequence contexts correlated strongly with G --> T transversion hotspots in spontaneous mutational spectra reported for the Escherichia coil lad and human p53 and factor LY genes. We present an example directly linking the interplay between DNA repair and replication to a ''high risk sequence'' for base substitution.

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Documento generato il 15/07/20 alle ore 08:13:11