Enzymes that belong to the NUDT (Nudix) superfamily catalyze the hydrolysis of phosphodiester bonds in molecules including nucleoside triphosphates and diphosphates and nucleotide sugars. Family members are defined by the presence of an amino acid sequence motif shared with the E. coli MutT gene product, and are involved in diverse physiological processes (Mildvan et al. 2005; McLennan 2006).
The hydrolysis of nucleoside di and triphosphates whose purine bases have been oxidized or deaminated may protect the cell from the mutational damage that would occur if modified deoxyribonucleotides were incorporated into DNA and from the aberrant protein synthesis that would occur if modified ribonucleotides were incorporated into mRNA (Iyama et al. 2010; Takagi et al. 2012). The hydrolysis of ADP ribose may prevent the aberrant spontaneous ADP ribosylation of cellular proteins that could occur were this molecule to accumulate to high levels in the cell (Perraud et al. 2003; Shen et al. 2003). This hypothesis is further supported by the demonstration that mice lacking NUDT1 show an increased lifetime incidence of liver and other tumors compared to normal controls, and that rapidly metabolizing tumor cells in culture are killed under conditions where synthesis of NUDT1 protein is suppressed or its catalytic activity is inhibited (Gad et al. 2014; Huber et al. 2014).