In identifying DYNLL1 and ASCIZ as essential mediators of 53BP1-dependent PARPi sensitivity in Brca1-deficient cancer cells, our findings provide a molecular explanation for the identification of both proteins as PARPi resistance factors in BRCA1-deficient cells in recently published genetic screens48,49, and reveal a previously unanticipated mechanism in which 53BP1 misregulation could lead to PARPi resistance in the clinic. The gene discussed is TP53BP1; the disease is cancer.