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Lookup NU author(s): Professor Alexander Burkle
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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 2001. © 2001 John Wiley and Sons, Inc.
Author(s): Burkle A
Publication type: Review
Publication status: Published
Journal: BioEssays
Year: 2001
Volume: 23
Issue: 9
Pages: 795-806
ISSN (print): 0265-9247
ISSN (electronic): 1521-1878
URL: http://dx.doi.org/10.1002/bies.1115
DOI: 10.1002/bies.1115
PubMed id: 11536292
