The multifaceted roles of PARP1 in DNA repair and chromatin remodelling

Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers...

Despite more than 50 years of research, the vast majority of the biology of poly(ADP-ribosyl)ation (PARylation) still remains a gross mystery. Originally described to be a part of the DNA repair machinery, poly(ADP-ribose) (PAR) is synthesized immediately by poly(ADP-ribose) polymerases (PARPs, also known as ARTDs) upon DNA damage and then rapidly removed by degrading enzymes. PAR provides a delicate and spatiotemporal interaction scaffold for numerous target proteins. Thus, the multifaceted PARylation system, consisting of PAR itself and its synthesizers and erasers, plays diverse roles in the DNA damage response (DDR), in DNA repair, transcription, replication, chromatin remodelling, metabolism and cell death...