The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy

Abstract

DNA damage is a deleterious threat, but occurs daily in all types of cells. In response to DNA damage, poly(ADP-ribosyl)ation, a unique post-translational modification, is immediately catalyzed by poly(ADP-ribose) polymerases (PARPs) at DNA lesions, which facilitates DNA damage repair. Recent studies suggest that poly(ADP-ribosyl)ation is one of the first steps of cellular DNA damage response and governs early DNA damage response pathways. Suppression of DNA damage-induced poly(ADP-ribosyl)ation by PARP inhibitors impairs early DNA damage response events. Moreover, PARP inhibitors are emerging as anti-cancer drugs in phase III clinical trials for BRCA-deficient tumors. In this review, we discuss recent findings on poly(ADP-ribosyl)ation in DNA damage response as well as the molecular mechanism by which PARP inhibitors selectively kill tumor cells with BRCA mutations.