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

J Mol Biol. 2020 Mar 13;432(6):1769-1791. doi: 10.1016/j.jmb.2019.12.019. Epub 2019 Dec 20.

Abstract

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. In this review, the roles of PARP-mediated modifications of protein and nucleic acids, the readers of ADP-ribosylated structures, and the origin and function of programmed DNA strand breaks in PARP activation, transcription regulation, and DNA demethylation are discussed.

Keywords: DNA and RNA ADP-ribosylation; DNA demethylation; programmed DNA breaks; readers of ADP-ribosylated targets; regulation of transcription.

Publication types

  • Review