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The regulation of chromatin state and histone protein eviction have been proven essential during transcription and DNA repair. Poly(ADP-ribose) (PAR) polymerase 1 (PARP-1) and poly(ADP-ribosyl)ation (PARylation) are crucial mediators of these processes by affecting DNA/histone epigenetic events. DNA methylation/hydroxymethylation patterns and histone modifications are established by mutual coordination between all epigenetic modifiers. This review will focus on histones and DNA/histone epigenetic machinery that are direct targets of PARP-1 activity by covalent and non-covalent PARylation. The effects of these modifications on the activity/recruitment of epigenetic enzymes at DNA damage sites or gene regulatory regions will be outlined. Furthermore, based on the achievements made to the present, we will discuss the potential application of epigenetic-based therapy as a novel strategy for boosting the success of PARP inhibitors, improving cell sensitivity or overcoming drug resistance.

Epigenetic Insights on PARP-1 Activity in Cancer Therapy