LIG1 is a synthetic lethal target in BRCA1 mutant cancers.

Synthetic lethality approaches in BRCA1/2-mutated cancers have focused on poly(ADP-ribose) polymerase (PARP) inhibitors, which are subject to high rates of innate or acquired resistance in patients. Here, we used CRISPR/Cas9-based screening to identify DNA Ligase I (LIG1) as a novel target for synthetic lethality in BRCA1-mutated cancers. Publicly available data supported LIG1 hyperdependence of BRCA1-mutant cells across a variety of breast and ovarian cancer cell lines.