“…Surprisingly, phosphomimetic mutations of T592 abolish the antiretroviral activity, but do not affect dNTP hydrolysis in vitro or in cells, which raises questions about the exact relationship between dNTP depletion and the restriction of retroviral replication 23 , 25 , 27 . It is also unclear whether and how the dNTPase activity contributes to other, less well-understood biological functions of SAMHD1, such as its roles in the DNA double-strand break repair 35 , interferon signaling 36 – 38 , restriction of LINE-1 retroelements 39 – 41 , degradation of nascent DNA at stalled replication forks 42 , and posttranscriptional control of mRNAs in regulatory T cells 43 . Involvement of nucleic acids in these distinct cellular activities suggests that the interaction of SAMHD1 with nucleic acids 44 – 49 may contribute to its function.…”