PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central important functions PARP enzymes in DNA damage response nucleosome remodelling. Activation happens through binding via zinc fingers and/or WGR domain. Modulation their activity inhibitors occupying site has proven successful cancer therapies. For decades, studies set out elucidate full-length molecular structure activation mechanism. In last five years, significant advances have progressed structural functional understanding PARP1-3, such allosteric inter-domain contacts, how senses damaged crowded nucleus, complementary role histone PARylation factor 1 modulating active PARP. Here, we review these together with versatility domains involved binding, shape PARPs