Collectively, these findings suggest that loss of PARP1 replication activity due to PARPi, PARP1 deletion or FANCJ loss is toxic to BRCA1 deficient cells (Fig. 5f) predicting that PARPi efficacy in BRCA mutant cancer derives from loss of PARP1 S-phase activity and not PARP1 trapping. The gene discussed is BRCA1; the disease is cancer.