96 SAMHD1 has been observed as a restriction factor for HIV-1 infection by suppressing cGAS activity to limit innate and adaptive immune responses.135 Mechanistically, SAMHD1 facilitates clearance of naked DNA at stalled replication forks.136 In SAMHD1-deficient cells, cytosolic DNA accumulates to trigger the production of interferons, and this depends on MRE11 and RECQ1.136 Considering that SAMHD1 is frequently mutated in AGS and some cancer, it is plausible that inhibition of MRE11 and/or RECQ1 would attenuate cGAS activation through reducing the production of DNA fragments. The gene discussed is CGAS; the disease is cancer.