Cells react to stress by alerting a variety of well known defense and repair mechanisms. A mystery so far is how the alarm is turned off. In two recent studies, we have now identified crucial enzymes involved in this process, and if one of them is missing it causes a serious neurodegenerative disease.
We identified a family of macrodomain enzymes present in viruses, yeast and animals that reverse cellular ADP-ribosylation by acting on mono-ADP-ribosylated substrates. Our discoveries establish the complete reversibility of PARP-catalyzed cellular ADP-ribosylation as a regulatory modification.