Activation of PARP2/ARTD2 by DNA damage induces conformational changes relieving enzyme autoinhibition

Abstract Human PARP2/ARTD2 is an ADP-ribosyltransferase which, when activated by 5?-phosphorylated DNA ends, catalyses poly-ADP-ribosylation of itself, other proteins and DNA. In this study, a crystal structure PARP2 in complex with activating shows that the WGR domain bridges dsDNA gap joins ends. This binding results major conformational changes, including reorganization helical fragments, regulatory domain. A comparison PARP1 structures reveals how to damage site leads formation catalytically competent conformation. conformation, capable substrate NAD + histone PARylation factor 1 changes residue specificity from glutamate serine initiating repair processes. The also autoinhibitory would promote flexibility needed enzyme reach target macromolecule for ADP-ribosylation.