Multiple groups of ADP-ribose moieties can also be transferred to proteins to form long branched chains, in a reaction called poly(ADP-ribosyl)ation. This protein modification is carried out by the poly ADP-ribose polymerases (PARPs), which are found in most eukaryotes, but not prokaryotes or yeast. The poly(ADP-ribose) structure is involved in the regulation of several cellular events and is most important in the cell nucleus, in processes such as DNA repair and telomere maintenance.
ADP-ribosylation is also responsible for the actions of some bacterial toxins, such as cholera toxin, diphtheria toxin, pertussis toxin, and heat-labile enterotoxin. These toxin proteins are ADP-ribosyltransferases that modify target proteins in human cells. For example, cholera toxin ADP-ribosylates G proteins, causing massive fluid secretion from the lining of the small intestine, resulting in life-threatening diarrhea. P. aeruginosa ADP-ribosylates cytoskeleton and GTP-binding proteins.