Finally, given that SAMHD1 depletion and proteasomal degradation sensitizes cancer cells to IR, PARP inhibitor, and other DSB-inducing agents69, our findings provide mechanistic rationale for targeting the end resection function of SAMHD1 through SIRT1 inhibition as an adjunct to DSB-inducing agents for cancer therapy. Here, SAMHD1 is linked to cancer.