BRCA2 is epistatic to the RAD51 paralogs in response to DNA damage

► BRCA2 and the RAD51 paralogs were down-regulated in human cells using siRNA. ► Epistatic interactions were examined by cellular responses to mitomycin C. ► BRCA2 knockdown imparts greater sensitivity than any individual RAD51 paralog. ► BRCA2 is epistatic to RAD51B, RAD51C, RAD51D, and XRCC3. ► BRCA2 and RAD51 paralog knockdown results in loss of viability in U2OS cells.