Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine nucleotides.
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 Km of 32 microM. 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.
Cai
Jian-Ping
JP
Department of Biology and Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan.
Ishibashi
Toru
T
Takagi
Yasumitsu
Y
Hayakawa
Hiroshi
H
Sekiguchi
Mutsuo
M
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003848:Deoxyguanine Nucleotides / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics; D011755:Pyrophosphatases; D016415:Sequence Alignment
D003848:Deoxyguanine Nucleotides; D029968:Escherichia coli Proteins; C078206:8-oxodeoxyguanosine triphosphate; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C052211:mutT protein, E coli; C475692:Nudt15 protein, mouse