Insight into DNA substrate specificity of PARP1-catalysed DNA poly(ADP-ribosyl)ation.

DNA-dependent poly(ADP-ribose) polymerases (PARPs) PARP1, PARP2 and PARP3 act as DNA break sensors signalling DNA damage. Upon detecting DNA damage, these PARPs use nicotine adenine dinucleotide as a substrate to synthesise a monomer or polymer of ADP-ribose (MAR or PAR, respectively) covalently attached to the acceptor residue of target proteins. Recently, it was demonstrated that PARP1-3 proteins can directly ADP-ribosylate DNA breaks by attaching MAR and PAR moieties to terminal phosphates.

Role of PARP-catalyzed ADP-ribosylation in the Crosstalk Between DNA Strand Breaks and Epigenetic Regulation.

Covalent linkage of ADP-ribose units to proteins catalyzed by poly(ADP-ribose) polymerases (PARPs) plays important signaling functions in a plethora of cellular processes including DNA damage response, chromatin organization, and gene transcription. Poly- and mono-ADP-ribosylation of target macromolecules are often responsible both for the initiation and for coordination of these processes in mammalian cells. Currently, the number of cellular targets for ADP-ribosylation is rapidly expanding, and the molecular mechanisms underlying the broad substrate specificity of PARPs present enormous interest.