Functional correlation between WRN and SAMHD1 in end-resection

Double-strand breaks (DSBs) can cause chromosome rearrangements, leading to cancer and some genetic diseases. WRN and SAMHD1 are proteins implicated in DSB processing and form a complex. Our study shows that SAMHD1 influences the nuclear recruitment of WRN in response to CPT-induced DSBs. Silencing SAMHD1 restores single-stranded DNA formation in WRN-deficient cells. However, DSB accumulation from CPT treatment is not recovered in WRN S1133A or WS cells when SAMHD1 is silenced. This suggests SAMHD1 cooperates with WRN in DNA damage repair and may have additional protective roles when WRN function in DSBs processing is impaired.