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 (PubMed:
19525956, PubMed:
21613998, PubMed:
21720370, PubMed:
23602554, PubMed:
23601106, PubMed:
22056990, PubMed:
24336198, PubMed:
26294762, PubMed:
26431200, PubMed:
28229507, PubMed:
28834754, PubMed:
29670289). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: 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 (PubMed:
19525956, PubMed:
21613998, PubMed:
21720370, PubMed:
23602554, PubMed:
23601106, PubMed:
23364794, PubMed:
25038827, PubMed:
26101257, PubMed:
22056990, PubMed:
24336198, PubMed:
28229507, PubMed:
26294762, PubMed:
26431200). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:
24035396, PubMed:
29610582, PubMed:
24217394). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed:
21613998, PubMed:
21720370). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed:
23858451). Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (PubMed:
23602554, PubMed:
23601106, PubMed:
29610582, PubMed:
29670289). 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). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (PubMed:
27477283, PubMed:
29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:
29670289). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity).
