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In vitro dNTPase activity of SAMHD1 is altered by cancer-associated mutations. Purified SAMHD1 (A) and SAMHD1 mutant proteins V133I (B), A338T (C), R366H (D), and D497Y (E) were incubated with 1 mM dCTP, dTTP, dATP, or dGTP separately with 1 mM GTP as the activator, and the deoxynucleoside products (dC, dT, dA, and dG) were analyzed by HPLC. Numbers indicate detected deoxynucleoside products in mutants compared with WT SAMHD1. Error bars indicate SD. nd, not detectable.
