Regulation of chromatin structure and function by PARP-1 and ADP-ribosylation

Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that catalyzes the transfer of ADP-ribose units from nicotinamide adenine dinucleotide (NAD⁺) to a variety of target proteins to regulate their activities and functions. Numerous studies over the past three decades have uncovered a close functional relationship between PARP-1 and chromatin during gene regulation and DNA repair. Recent studies have begun to reveal the underlying mechanisms of this functional interplay, including the role of DNA structures, histone modifications and variants, the chromatin-regulating machinery, cellular signaling pathways, and specific features of PARP-1 itself. The picture of PARP-1 that has emerged is of a multifunctional chromatin regulatory protein that can serve as an interface between external and internal cues, and the fundamental processes that control the biology of the genome. These studies have increased our understanding of the roles of PARP-1 in physiological and pathological processes from stress responses and inflammation to metabolism and apoptosis. In this chapter, we discuss how PARP-1 and ADP-ribosylation regulate chromatin structure and function to control a variety of nuclear processes, as well as downstream biological responses.