The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases

Front Biosci. 2008 Jan 1;13:3046-82. doi: 10.2741/2909.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Diphosphate / chemistry
  • Animals
  • Cell Death
  • Chromatin / chemistry
  • Chromatin Immunoprecipitation
  • Crystallization
  • Humans
  • Mass Spectrometry / methods
  • Mice
  • Mice, Transgenic
  • Multigene Family
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / physiology*
  • Protein Binding
  • Protein Isoforms
  • Ribose / chemistry

Substances

  • Chromatin
  • Protein Isoforms
  • Adenosine Diphosphate
  • Ribose
  • Poly(ADP-ribose) Polymerases