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

8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is produced by active oxygen species in the nucleotide pool of the cell and can be incorporated into cellular DNA. Human cells contain enzyme activity that hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing occurrence of mutations, caused by misincorporation. When the cDNA for human 8-oxo-dGTPase was expressed in Escherichia coli mutT(-) mutant cells devoid of self 8-oxo-dGTPase activity, the elevated level of spontaneous A:T to C:G mutation frequency reverted to normal. We isolated the genomic sequence encoding the enzyme and named the gene MTR1 (for mutT human homologue). This gene is composed of at least 4 exons, spans approximately 9 kb, and is located on human chromo some 7p22. (C) 1994 Academic Press,Inc