Disease relevance of Nudt1

• 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 [1].

High impact information on Nudt1

• When lysine-38 was replaced by other amino acids, all of the mutants isolated carried the 8-oxo-dGTPase-negative phenotype [2].
• Organisms possess an enzyme, 8-oxo-dGTPase, which catalyzes the hydrolysis of 8-oxo-dGTP to the corresponding nucleoside monophosphate, thereby preventing the occurrence of mutation [2].
• 8-Oxo-dGTPase-positive revertants, isolated from one of the negative mutants, carried the codon for lysine [2].
• To verify this finding in a relevant animal model, we investigated the effects of Cd(II) on cellular 8-oxo-dGTPase activity and nuclear DNA 8-oxo-dG levels in the rat testis, a target organ for Cd(II) carcinogenesis [3].
• We previously found that Cd(II) inhibited 8-oxo-dGTPase in both cell free systems and cultured cells [3].

Biological context of Nudt1

• The predicted amino acid sequence of the rat 8-oxo-dGTPase has a close homology with those of human and bacterial counterparts [1].
• The nucleotide sequence of the cDNA revealed that the rat 8-oxo-dGTPase protein is composed of 156 amino acid residues [1].
• 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 [1].
• 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 [1].

Anatomical context of Nudt1

• Cadmium(II), unlike nickel(II), inhibits 8-oxo-dGTPase activity and increases 8-oxo-dG level in DNA of the rat testis, a target organ for cadmium(II) carcinogenesis [3].
• After developing an assay for 8-oxo-dGTPase activity, we confirmed the inhibition by Cd(II) in cultured cells and in the rat testis, the target organ for cadmium carcinogenesis [4].

Associations of Nudt1 with chemical compounds

• cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides [1].
• 8-Oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) is an enzyme which prevents incorporation into DNA of promutagenic 8-oxo-2'-deoxyguanosine (8-oxo-dG) from a deoxynucleotide pool damaged by endogenous oxidants [3].
• Formation of 8-OH-dG in DNA and 8-oxo-dGTPase mRNA expression were also increased at these time points, the amounts of malondialdehyde and 4-hydroxy-2-nonenal showed 2 peaks at 6 hr and 3 days [5].

References