The nicotinamide hypothesis revisited-plant defense signaling integrating PARP, nicotinamide, nicotinic acid, epigenetics, and glutathione.

A previously presented hypothesis, here updated, proposed nicotinamide produced by the activity of poly(ADP-ribose) polymerase (PARP) as a stress signaling compound in plants. PARP activation by DNA strand breaks caused by oxidative stress leads to the metabolization of NAD to ADP-ribose units and nicotinamide. Also, NAD-degrading histone deacetylases (sirtuins) produce nicotinamide. We suggest that nicotinamide, either alone or acting through its metabolite nicotinic acid, will generate epigenetic changes in the plant. We propose that this is an early step in a general stress response, making the DNA more accessible to the transcription machinery and specific stress signaling substances to activate the defense genes needed for the present stress situation. The role of glutathione in this context is discussed.