PARP-1 is an abundant (~1 to 2 million molecules per cell) and ubiquitous nuclear protein that plays important roles in a variety of cellular functions. One aspect of PARP-1 biology is the modulation of chromatin structure through direct nucleosome binding, covalent modification of chromatin proteins, or the production of PAR which can serve as a polyanionic matrix for the binding of chromatin proteins. Given its role in a variety of physiological and pathophysiological processes, PARP-1 has become an attractive target for drug-based therapies. Although the role of PARP-1's nucleosome-binding and chromatin-modulating activities in PARP-1-dependent DNA repair, cell death, and inflammatory response pathways have not yet been defined, they are likely to play a critical role. Continued biochemical and cell-based studies will help to clarify PARP-1's role as a chromatin-modulating protein, as well as elucidate new ways to target PARP-1 for the treatment of disease.
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