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Physiology and pathophysiology of poly(ADP‐ribosyl)ation *
Author(s) -
Bürkle Alexander
Publication year - 2001
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.1115
Subject(s) - poly adp ribose polymerase , nad+ kinase , dna repair , polymerase , biology , dna damage , pathophysiology , ribose , telomere , dna , biochemistry , chemistry , microbiology and biotechnology , enzyme , endocrinology
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. BioEssays 23:795–806, 2001. © 2001 John Wiley & Sons, Inc.