Recently, a genome-wide CRISPR knockout screen identified USP1 to be selective essential in breast & ovarian cancer cell lines harboring HRD, especially BRAC1/2 deficiency.331 It is prospected that BRCA1 deficient cells was characterized by fork instability and cannot tolerate more instabilities by the absence of active USP1.330 By mechanism persistent monoubiquitinated PCNA was responsible for synthetic lethal relationship between USP1 and BRCA1. The gene discussed is BRCA1; the disease is ovarian carcinoma.