ARTD1 (PARP1) activation and NAD(+) in DNA repair and cell death

DNA Repair (Amst). 2014 Nov;23:27-32. doi: 10.1016/j.dnarep.2014.09.004. Epub 2014 Oct 3.

Abstract

Nicotinamide adenine dinucleotide, NAD(+), is a small metabolite coenzyme that is essential for the progress of crucial cellular pathways including glycolysis, the tricarboxylic acid cycle (TCA) and mitochondrial respiration. These processes consume and produce both oxidative and reduced forms of NAD (NAD(+) and NADH). NAD(+) is also important for ADP(ribosyl)ation reactions mediated by the ADP-ribosyltransferase enzymes (ARTDs) or deacetylation reactions catalyzed by the sirtuins (SIRTs) which use NAD(+) as a substrate. In this review, we highlight the significance of NAD(+) catabolism in DNA repair and cell death through its utilization by ARTDs and SIRTs. We summarize the current findings on the involvement of ARTD1 activity in DNA repair and most specifically its involvement in the trigger of cell death mediated by ARTD1 activation and energy depletion. By sharing the same substrate, the activities of ARTDs and SIRTs are tightly linked, are dependent on each other and are thereby involved in the same cellular processes that play an important role in cancer biology, inflammatory diseases and ischaemia/reperfusion.

Keywords: ADP(ribosyl)ation; Energy depletion; Metabolic defects; NAD(+).

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Death / genetics
  • DNA Damage
  • DNA Repair / physiology*
  • Enzyme Activation
  • Glycolysis
  • Humans
  • Metabolic Networks and Pathways
  • NAD / metabolism*
  • Oxidation-Reduction
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Sirtuins / metabolism

Substances

  • NAD
  • Poly Adenosine Diphosphate Ribose
  • PARP1 protein, human
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Sirtuins