Physiology and pathophysiology of poly(ADP-ribosyl)ation

Bioessays. 2001 Sep;23(9):795-806. doi: 10.1002/bies.1115.


One of the immediate eukaryotic cellular responses to DNA breakage is the covalent post-translational modification of nuclear proteins with poly(ADP-ribose) from NAD+ as precursor, mostly catalysed by poly(ADP-ribose) polymerase-1 (PARP-1). Recently several other polypeptides have been shown to catalyse poly(ADP-ribose) formation. Poly(ADP-ribosyl)ation is involved in a variety of physiological and pathophysiological phenomena. Physiological functions include its participation in DNA-base excision repair, DNA-damage signalling, regulation of genomic stability, and regulation of transcription and proteasomal function, supporting the previously observed correlation of cellular poly(ADP-ribosyl)ation capacity with mammalian life. The pathophysiology effects are mediated through PARP-1 overactivity, which can cause cell suicide by NAD+ depletion. It is apparent that the latter effect underlies the pathogenesis of a wide range of disease states including type-1 diabetes, ischaemic infarcts in various organs, and septic or haemorrhagic shock. Therefore pharmacological modulation of poly(ADP-ribosyl)ation may prove to be an exciting option for various highly prevalent, disabling and even lethal diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Cysteine Endopeptidases / genetics
  • DNA Damage
  • DNA Repair*
  • Diabetes Mellitus, Type 1 / enzymology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Gene Expression Regulation
  • Humans
  • Infarction / enzymology
  • Infarction / physiopathology
  • Models, Biological
  • Multienzyme Complexes / genetics
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Proteasome Endopeptidase Complex
  • Transcription, Genetic


  • Multienzyme Complexes
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex