New facets in the regulation of gene expression by ADP-ribosylation and poly(ADP-ribose) polymerases

The diverse subcellular locations and functions of poly(ADP-ribose) (PAR) and the members of the poly(ADPribose) Polymerase (PARP) family provide many opportunities to impact molecular processes and biological outcomes. The functions of the enzymatically active PARP family members are intimately tied to the nicotinamide adenine dinucleotide (NAD⁺) biosynthetic pathways, which provide a ready supply of ADPR units for catalysis and targeting, and underlie some of the functional interplay observed with other NAD⁺-utilizing enzymes. PARP proteins utilize NAD+ as a donor of ADP-ribose units and transfer these units to their target proteins. ADP-ribose transfer occurs at the catalytic domain of PARPs, which contains a donor s site with a PARP signature motif that binds NAD+ and an acceptor site where ADP-ribose chains are extended. Another layer of biological process that PAR modulates is protein degradation through ubiquitylation. greater understanding of the physiology and pathophysiology of PARPs will help us to target them more effectively, using PARP inhibitors as therapeutics.