Poly-ADP-ribosylation in health and disease

Abstract.

Poly(ADP-ribosyl)ation is a posttranslational modification of proteins in eukaryotic cells catalysed by a family of NAD⁺ ADP-ribosyl transferases, the poly(ADP-ribose) polymerases (PARPs). PARP-encoding genes now constitute a superfamily of at least 18 members encoding proteins that share homology with the catalytic domain of the founding member, PARP-1 [1]. Poly(ADP-ribose) metabolism is of central importance in a wide variety of biological processes including maintenance of genomic stability [2–4], DNA repair [3, 5], transcriptional regulation [6, 7], centromere function [8, 9], modulation of telomere length [10–12], regulation of proteasomal protein degradation [13, 14], regulation of endosomal vesicle trafficking [15, 16] and apoptosis [17, 18]. The life cycle of poly(ADP-ribose) is discussed in the following section. In addition, an overview of the genes and proteins involved in poly(ADP-ribose) metabolism and their possible cellular function is provided.