Our study additionallysupports the notion that EXO1i generate poly­(ADP-ribose)-decoratedDNA lesions during the S-phase that are associated with unresolvedDSBs and genomic instability in BRCA1-deficient but not in WT BRCA1cells., PARP inhibitors that were developed forthe treatment of cancers with HRD, such as BRCA1– and BRCA2–defective cancers, are a highly successful example of synthetic lethality(SL)., Deficiency in any of the homology-directedrepair genes has been found to lead to defective DSB repair, therebypromoting PARPi SL. The gene discussed is BRCA1; the disease is cancer.