Impact of a Cancer-Associated Mutation on Poly(ADP-ribose) Polymerase1 Inhibition.

Poly(ADP-ribose) polymerase1 (PARP1) plays a vital role in DNA repair and its inhibition in cancer cells may cause cell apoptosis. In this study, we investigated the effects of a PARP1 variant, V762A, which is strongly associated with several cancers in humans, on the inhibition of PARP1 by three FDA approved inhibitors: niraparib, rucaparib and talazoparib. Our work suggests that these inhibitors bind to the V762A mutant more effectively than to the wild-type (WT), with similar binding free energies between them.