ADPribosylaation

ADP-ribosylation is a post-translational modification in which ADP-ribose is transferred from NAD+ to target molecules, including proteins, nucleic acids, and small metabolites. This modification can occur as mono-ADP-ribosylation (MARylation), in which a single ADP-ribose is attached, or as poly-ADP-ribosylation (PARylation), in which ADP-ribose units are assembled into one or more chains.

Enzymes that catalyze this reaction are ADP-ribosyltransferases (ARTs). In eukaryotes, the poly(ADP-ribose) polymerases (PARPs) use NAD+ to build PAR chains on proteins, often in response to DNA damage. Bacterial and some archaeal toxins, such as diphtheria toxin and cholera toxin, are also ARTs that modify host proteins to alter signaling or metabolism. Substrates can include histones, metabolic enzymes, and, in some contexts, nucleic acids.

Mechanistically, MARylation involves transfer of a single ADP-ribose unit, while PARylation creates polymeric chains that can be long and branched. PAR chains are dynamic and reversible; they are removed by poly(ADP-ribose) glycohydrolase (PARG) and other ADP-ribosylhydrolases, whereas MAR groups are removed by specific hydrolases. The balance of installation and removal regulates many cellular processes.

Biological roles are diverse and include regulation of DNA repair, chromatin structure and transcription, signal transduction, and stress responses. PARP activity influences immune signaling and metabolism, while bacterial ARTs contribute to virulence. Clinically, PARP inhibitors are used to treat certain cancers (notably BRCA-mutant tumors) and are an active area of research for other diseases.