Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism

Poly(ADP-ribosyl)ation is a posttranslational modification that alters the functions of the acceptor proteins and is catalyzed by the poly(ADP-ribose) polymerase (PARP) family of enzymes. Following DNA damage, activated poly( ADP-ribose) polymerase-1 (PARP-1) catalyzes the elongation and branching of poly(ADP-ribose) (pADPr) covalently attached to nuclear target proteins. A lthough the biological role of poly(ADP-ribosyl)ation has not yet been defi ned, it has been implicated in many important cellular processes such as DN A repair and replication, modulation of chromatin structure, and apoptosis. The transient nature and modulation of poly(ADP-ribosyl)ation depend on th e activity of a unique cytoplasmic enzyme called poly(ADP-ribose) glycohydr olase which hydrolyzes pADPr bound to acceptor proteins in free ADP-ribose residues. While the PARP homologues have been recently reviewed, there are relatively scarce data about PARG in the literature. Here we summarize the latest advances in the PARG field, addressing the question of its putative nucleo-cytoplasmic shuttling that could enable the tight regulation of pADP r metabolism. This would contribute to the elucidation of the biological si gnificance of poly(ADP-ribosyl)ation. (C) 2001 Academic Press.