[Frontiers in Bioscience 13, 3046-3082, January 1, 2008]
The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases
Paul O. Hassa1, Michael O. Hottiger2
1European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Meyerhofstrasse 1, D-69117 Heidelberg, Germany, 2Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Winterthurerstrasse 190, 8057 Zurich, Switzerland
TABLE OF CONTENTS
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.