cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides

The enzyme, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase),is present In various organisms and plays an important rolein control of spontaneous mutagenesis. This enzyme degrades8-oxoguamne-contaning deoxyribonucleoside triphosphate, a potentiallymutagenic substrate for DNA synthesis, to the correspondingmonophosphate. To obtain appropriate probes for expression ofthe gene in various tissues and also to construct appropriateexperimental models for carcino genesis, we cloned cDNA forrat 8-oxo-dGTPase and elucidated its structure. The nucleotidesequence of the cDNA revealed that the rat 8-oxo-dGTPase proteinis composed of 156 amino acid residues. The molecular weightof rat 8-oxo-dGTPase, calculated from the predicted amino acidse was 18 006, and the 8-oxo-dGTPase protein of this size wasdetected when the cDNA was expressed in 8-oxo-dGTPase-deficlentEscherichitz coil mutT^– cells. The predicted amino acidsequence of the rat 8-oxo-dGTPase has a close homology withthose of human and bacterial counterparts. Using the cDNA asa probe, part of the rat gene for 8-oxo-dGTPase was isolatedand was found to consist of at least three exons and spannedabout 10 kb. A genomic region containing the pseudogene wasalso isolated.