May catalyze the hydrolysis of nucleoside triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP and the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP (PubMed:26238318). Could also catalyze the hydrolysis of some nucleoside diphosphate derivatives (PubMed:22556419, PubMed:26238318). Hydrolyzes oxidized nucleosides triphosphates like 8-oxo-dGTP in vitro, but the specificity and efficiency towards these substrates are low. Therefore, the potential in vivo sanitizing role of this enzyme, that would consist in removing oxidatively damaged forms of nucleosides to prevent their incorporation into DNA, is unclear (PubMed:26238318, PubMed:22556419). Through the hydrolysis of thioguanosine triphosphates may participate in the catabolism of thiopurine drugs (PubMed:26238318, PubMed:25108385). May also have a role in DNA synthesis and cell cycle progression by stabilizing PCNA (PubMed:19419956). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (By similarity). a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-phosphate + diphosphate + H(+) a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-deoxyribonucleoside 5'-phosphate + diphosphate + H(+) a 5'-end CoA-ribonucleoside in mRNA + H2O = (R)-4'-phosphopantetheine + a 5'-end phospho-adenosine-phospho-ribonucleoside in mRNA + 2 H(+) Magnesium may be the real cofactor in vivo. Has a 10-fold higher catalytic efficiency toward dGTP compared to 8-oxo-dGTP. Homodimer (PubMed:26238318). Interacts with PCNA; interaction is disrupted in response to UV irradiation (PubMed:19419956). Polymorphic NUDT15 variants define the poor metabolism of thiopurines 2 genetic locus (THPM2) [MIM:616903]. Thiopurines are used as immunosuppressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with low NUDT15 activities have an increased risk for toxic effects after receiving standard doses of thiopurine drugs. Belongs to the Nudix hydrolase family.