NUDT1 hydrolyses 2-OH-dATP to 2-OH-dAMP 2-hydroxy-dATP + H2O => 2-hydroxy-dAMP + PPi Authored: D'Eustachio, P, 2012-07-06 Edited: D'Eustachio, P, 2012-07-06 NUDT1 (MTH1) catalyzes the reaction of 2-hydroxy-dATP and water to form 2-hydroxy-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 2-hydroxy-dATP (Fujikawa et al. 1993; Sakai et al. 2002). 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 (Yoshimura et al. 2003). Together, these data support the hypothesis that by cleaving 2-hydroxy-dATP and thus preventing its incorporation into DNA, NUDT1 provides a physiologically important defense against mutagenesis due to oxidative stress. Pubmed10373420 Pubmed10536140 Pubmed11756418 Pubmed12857738 Pubmed15133035 Pubmed7782328 Reactome Database ID Release 432395818 Reactome, http://www.reactome.org ReactomeREACT_150363 Reviewed: Ito, Riyoko, 2012-10-05