## Abstract Poly(ADP‐ribose) polymerases are involved in many aspects of regulation of cellular functions. Using NAD^+^ as a substrate, they catalyse the covalent transfer of ADP‐ribose units onto several acceptor proteins to form a branched ADP‐ribose polymer. The best characterised and first disc
Physiology and pathophysiology of poly(ADP-ribosyl)ation
✍ Scribed by Alexander Bürkle
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 247 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0265-9247
No coin nor oath required. For personal study only.
✦ Synopsis
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.
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