Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (By similarity). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (By similarity). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of mre11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (PubMed:29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289). a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-deoxyribonucleoside + H(+) + triphosphate Binds 1 zinc ion per subunit. Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. Allosteric activation promotes the formation of highly active homotetramers. Homodimer; in absence of GTP and dNTP (By similarity). Homotetramer; in GTP- and dNTP-bound form (By similarity). Interacts with rbbp8/CtIP (PubMed:29670289). Localizes to sites of DNA double-strand breaks in response to DNA damage. Belongs to the SAMHD1 family.