Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine nucleotides

被引:97
作者
Cai, JP
Ishibashi, T
Takagi, Y
Hayakawa, H
Sekiguchi, M
机构
[1] Fukuoka Dent Coll, Dept Biol, Fukuoka 8140193, Japan
[2] Fukuoka Dent Coll, Frontier Res Ctr, Fukuoka 8140193, Japan
[3] Kyushu Univ, Grad Sch Med Sci, Dept Med Biochem, Fukuoka 8128582, Japan
关键词
oxygen radical; mutation; MutT; 8-oxoguanine; MTH2;
D O I
10.1016/S0006-291X(03)00864-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MutT-related proteins degrade 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), a mutagenic substrate for DNA synthesis, in the nucleotide pool, thereby preventing DNA replication errors. During a search of GenBank EST database, we found a new member of MutT-related protein, MTH2, which possesses the 23-amino acid MutT module. The cloned mouse MTH2 (mMTH2) cDNA was expressed in Escherichia coli mutT(-) cells and the protein was purified. mMTH2 protein hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP. with Kin of 32 muM. Expression of cDNA for mMTH2 reduced significantly the elevated level of spontaneous mutation frequency of E. coli mutT- cells. Thus, MTH2 has a potential to protect the genetic material from the untoward effects of endogenous oxygen radicals. MTH2 could act as an MTH1 redundancy factor. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:1073 / 1077
页数:5
相关论文
共 22 条
[1]   DIETARY CARCINOGENS AND ANTICARCINOGENS - OXYGEN RADICALS AND DEGENERATIVE DISEASES [J].
AMES, BN .
SCIENCE, 1983, 221 (4617) :1256-1264
[2]   ESCHERICHIA-COLI MUTY GENE-PRODUCT IS REQUIRED FOR SPECIFIC A-G-]C.G MISMATCH CORRECTION [J].
AU, KG ;
CABRERA, M ;
MILLER, JH ;
MODRICH, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (23) :9163-9166
[3]  
BESSHO T, 1993, J BIOL CHEM, V268, P19416
[4]   The MutT proteins or ''nudix'' hydrolases, a family of versatile, widely distributed, ''housecleaning'' enzymes [J].
Bessman, MJ ;
Frick, DN ;
OHandley, SF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (41) :25059-25062
[5]   OXIDATIVE STRESS RESPONSES IN ESCHERICHIA-COLI AND SALMONELLA-TYPHIMURIUM [J].
FARR, SB ;
KOGOMA, T .
MICROBIOLOGICAL REVIEWS, 1991, 55 (04) :561-585
[6]   Functional significance of the conserved residues for the 23-residue module among MTH1 and MutT family proteins [J].
Fujii, Y ;
Shimokawa, H ;
Sekiguchi, M ;
Nakabeppu, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (53) :38251-38259
[7]   The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein [J].
Fujikawa, K ;
Kamiya, H ;
Yakushiji, H ;
Fujii, Y ;
Nakabeppu, Y ;
Kasai, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (26) :18201-18205
[8]   GENOMIC STRUCTURE AND CHROMOSOME LOCATION OF THE HUMAN MUTT HOMOLOG GENE MTH1 ENCODING 8-OXO-DGTPASE FOR PREVENTION OF A-T TO C-G TRANSVERSION [J].
FURUICHI, M ;
YOSHIDA, MC ;
ODA, H ;
TAJIRI, T ;
NAKABEPPU, Y ;
TSUZUKI, T ;
SEKIGUCHI, M .
GENOMICS, 1994, 24 (03) :485-490
[9]  
HALLIWELL B, 1991, FEBS LETT, V1, P9
[10]   Potential of Escherichia coli GTP cyclohydrolase II for hydrolyzing 8-oxo-dGTP, a mutagenic substrate for DNA synthesis [J].
Kobayashi, M ;
Ohara-Nemoto, Y ;
Kaneko, M ;
Hayakawa, H ;
Sekiguchi, M ;
Yamamoto, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) :26394-26399