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Bioessays. 2001 Sep;23(9):795-806.

Physiology and pathophysiology of poly(ADP-ribosyl)ation.

Author information

1
Department of Gerontology, Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne, NE4 6BE, UK. Alexander.Buerkle@ncl.ac.uk

Abstract

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.

PMID:
11536292
DOI:
10.1002/bies.1115
[Indexed for MEDLINE]

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