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 role in control of spontaneous mutagenesis. This enzyme degrades 8-oxoguanine-containing deoxyribonucleoside triphosphate, a potentially mutagenic substrate for DNA synthesis, to the corresponding monophosphate. To obtain appropriate probes for expression of the gene in various tissues and also to construct appropriate experimental models for carcinogenesis, we cloned cDNA for rat 8-oxo-dGTPase and elucidated its structure. The nucleotide sequence of the cDNA revealed that the rat 8-oxo-dGTPase protein is composed of 156 amino acid residues. The molecular weight of rat 8-oxo-dGTPase, calculated from the predicted amino acid sequence, was 18 006, and the 8-oxo-dGTPase protein of this size was detected when the cDNA was expressed in 8-oxo-dGTPase-deficient Escherichia coli mutT(-) cells. The predicted amino acid sequence of the rat 8-oxo-dGTPase has a close homology with those of human and bacterial counterparts. Using the cDNA as a probe, part of the rat gene for 8-oxo-dGTPase was isolated and was found to consist of at least three exons and spanned about 10 kb. A genomic region containing the pseudogene was also isolated.