MOUSE MTH1 PROTEIN WITH 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE 5'-TRIPHOSPHATASE ACTIVITY THAT PREVENTS TRANSVERSION MUTATION - CDNA CLONING AND TISSUE DISTRIBUTION

8-Oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is fo rmed in the nucleotide pool of a cell during normal cellular metabolis m, and when it is incorporated into DNA causes mutation. Organisms pos sess 8-oxo-dGTPase, an enzyme that specifically degrades 8-oxo-dGTP to 8-oxo-dGMP. We isolated cDNA for mouse 8-oxo-dGTPase, using as a prob e human MTH1 (Escherichia coli mutT homolog) cDNA. The nucleotide sequ ence of the cDNA revealed that the mouse MTH1 protein (molecular weigh t of 17,896) comprises 156 amino acid residues. When the cDNA for mous e 8-oxo-dGTPase was expressed in E. coli mutT(-) mutant cells devoid o f their own 8-oxo-dGTPase activity, an 18-kDa protein, which is cross- reactive with an anti-human MTH1 antibody, was formed. In such cells, the level of spontaneous mutation frequency that was elevated reverted to normal. High levels of 8-oxo-dGTPase activity were found in liver, thymus, and large intestine, whereas all other organs examined contai ned smaller amounts of the enzyme. In embryonic stem cells, an exceedi ngly high level of the enzyme was present.