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Titolo:
Distribution of spontaneous CpG-associated G : C -> A : T mutations in thelacZ gene of Muta (TM) mice: Effects of CpG methylation, the sequence context of CpG sites, and severity of mutations on the activity of the lacZ gene product
Autore:
Ikehata, H; Takatsu, M; Saito, Y; Ono, T;
Indirizzi:
Tohoku Univ, Grad Sch Med, Div Genome & Radiat Biol, Dept Cell Biol,Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ Sendai Miyagi Japan 9808575 Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Dent, Dept Aging & Geriatr Dent, Sendai, Miyagi 980,Japan Tohoku Univ Sendai Miyagi Japan 980 eriatr Dent, Sendai, Miyagi 980,Japan
Titolo Testata:
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
fascicolo: 4, volume: 36, anno: 2000,
pagine: 301 - 311
SICI:
0893-6692(2000)36:4<301:DOSCG:>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESCHERICHIA-COLI; TRANSGENIC MICE; CYTOSINE DEAMINATION; DNA; TISSUE; MOUSE; 5-METHYLCYTOSINE; SPECTRUM; PROTOCOL; TARGET;
Keywords:
Muta mouse; transgenic mouse; DNA methylation; CpG; hotspot; spontaneous mutation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Ikehata, H Tohoku Univ, Grad Sch Med, Div Genome & Radiat Biol, Dept Cell Biol,Aoba Ku, Seiryo Machi 2-1, Sendai, Miyagi 9808575, Japan Tohoku Univ Seiryo Machi 2-1 Sendai Miyagi Japan 9808575 Japan
Citazione:
H. Ikehata et al., "Distribution of spontaneous CpG-associated G : C -> A : T mutations in thelacZ gene of Muta (TM) mice: Effects of CpG methylation, the sequence context of CpG sites, and severity of mutations on the activity of the lacZ gene product", ENV MOL MUT, 36(4), 2000, pp. 301-311

Abstract

In our previous study using transgenic Muta(TM) mice, G:C --> A:T transitions at 5'-CG-3' (CpG) sites, which are the most common mammalian spontaneous mutation, were detected in 197 of 330 spontaneous lacZ mutants. These transitions were recovered at only 27 of the 357 mutable G:C pairs within CpG sites where the transition could produce a missense or termination codon inthe lacZ gene. To address the underlying mechanism for the uneven distribution of mutated CpG sites, the CpG methylation status of the Muta lacZ genewas analyzed by a bisulfite method. All the CpG sites examined in the coding region were evenly methylated at a high level, and no site-specific methylation was evident. Analysis of the sequence context around the mutated CpG sites, however, revealed that 21 of these 27 sites contained a CpG Flanked by a pyrimidine on the 5' side, and that 187 of the 197 mutants resulted from substitutions at these sites. Moreover, we found five hotspots among those sites, the location of which was intimately related to the enzymatic activity of the gene product: one site produced a nonsense codon; three sites, one of which corresponded to the nucleophile at the active site, residedin the substrate-binding pocket; and the other site was located in a region conserved in the beta -galactosidase Family. These results strongly suggest that recovery of lacZ mutations at each site largely depend on the adjacent sequence context and the extent to which the mutation damages the enzymatic activity of the gene product. Environ. Mel. Mutagen. 36: 301-311, 2000. (C) 2000 Wiley-Liss, Inc.

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Documento generato il 08/04/20 alle ore 09:12:39