The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases.
Poly-ADP-ribose metabolism plays a mayor role in a wide range of biological processes, such as maintenance of genomic stability, transcriptional regulation, energy metabolism and cell death. Poly-ADP-ribose polymerases (PARPs) are an ancient family of enzymes, as evidenced by the poly-ADP-ribosylating activities reported in dinoflagellates and archaebacteria and by the identification of Parp-like genes in eubacterial and archaeabacterial genomes. Six genes encoding "bona fide" PARP enzymes have been identified in mammalians: PARP1, PARP2, PARP3, PARP4/vPARP, PARP5/Tankyrases-1 and PARP6/Tankyrases-2. The best studied of these enzymes PARP1 plays a primary role in the process of poly-ADP-ribosylation. PARP1-mediated poly-ADP-ribosylation has been implicated in the pathogenesis of cancer, inflammatory and neurodegenerative disorders. This review will summarize the novel findings and concepts for PARP enzymes and their poly-ADP-ribosylation activity in the regulation of physiological and pathophysiological processes. A special focus is placed on the proposed molecular mechanisms involved in these processes, such as signaling, regulation of telomere dynamics, remodeling of chromatin structure and transcriptional regulation. A potential functional cross talk between PARP family members and other NAD+-consuming enzymes is discussed.
Hassa
Paul O
PO
European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. hassa@embl.de
Hottiger
Michael O
MO
D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D016923:Cell Death; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D003460:Crystallization; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D020033:Protein Isoforms; D012266:Ribose / Q000737:chemistry
D002843:Chromatin; D020033:Protein Isoforms; D000244:Adenosine Diphosphate; D012266:Ribose; D011065:Poly(ADP-ribose) Polymerases