Meta-Biol

• Pathways

NUDT1 (MTH1) catalyzes the reaction of 8-oxo-dATP and water to form 8-oxo-dAMP and PPi (pyrophosphate). Four NUDT1 proteins have been identified, encoded by a single gene with alternative start codons (Oda et al. 1999). The shortest of these, NUDT1 p18, has been shown to catalyze hydrolysis of 8-oxo-dATP (Fujikawa et al. 2001). The active enzyme is a monomer associated with a magnesium ion (Mishima et al. 2004). The longer isoforms all consist of the p18 polypeptide with aminoterminal extensions and are presumed to be active as well, but have not been experimentally characterized. The p18 isoform is predominantly cytosolic (Kang et al. 1995). Its expression prevents the accumulation of modified adenosine bases in DNA in mutant mouse cells lacking endogenous NUDT1 activity, supporting the hypothesis that by cleaving 8-oxo-dATP and thus preventing its incorporation into DNA, NUDT1 provides a physiologically important defense against mutagenesis due to oxidative stress (Yoshimura et al. 2003).