PTIP associates with Artemis to dictate DNA repair pathway choice

PARP inhibitors (PARPi) are being used in patients with BRCA1/2 mutations; however, doubly deficient BRCA1−/−53BP1−/− tumors become resistant to PARPis. 53BP1 and its known downstream effectors, PTIP and RIF1, lack enzymatic activities directly implicated in DNA repair. Wang et al. uncovered a nuclease, Artemis, as a PTIP-binding protein that trims DNA ends, promotes NHEJ, and directly competes with the HR repair pathway. Loss of Artemis restores PARPi resistance in BRCA1-deficient cells.

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