This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hassa, P. O. Articles by Hottiger, M. O. Search for Related Content PubMed PubMed Citation Articles by Hassa, P. O. Articles by Hottiger, M. O.

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

Paul O. Hassa, Sandra S. Haenni, Michael Elser, and Michael O. Hottiger^*

Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland

Since poly-ADP ribose was discovered over 40 years ago, there has been significant progress in research into the biology of mono- and poly-ADP-ribosylation reactions. During the last decade, it became clear that ADP-ribosylation reactions play important roles in a wide range of physiological and pathophysiological processes, including inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. ADP-ribosylation reactions are phylogenetically ancient and can be classified into four major groups: mono-ADP-ribosylation, poly-ADP-ribosylation, ADP-ribose cyclization, and formation of O-acetyl-ADP-ribose. In the human genome, more than 30 different genes coding for enzymes associated with distinct ADP-ribosylation activities have been identified. This review highlights the recent advances in the rapidly growing field of nuclear mono-ADP-ribosylation and poly-ADP-ribosylation reactions and the distinct ADP-ribosylating enzyme families involved in these processes, including the proposed family of novel poly-ADP-ribose polymerase-like mono-ADP-ribose transferases and the potential mono-ADP-ribosylation activities of the sirtuin family of NAD⁺-dependent histone deacetylases. A special focus is placed on the known roles of distinct mono- and poly-ADP-ribosylation reactions in physiological processes, such as mitosis, cellular differentiation and proliferation, telomere dynamics, and aging, as well as "programmed necrosis" (i.e., high-mobility-group protein B1 release) and apoptosis (i.e., apoptosis-inducing factor shuttling). The proposed molecular mechanisms involved in these processes, such as signaling, chromatin modification (i.e., "histone code"), and remodeling of chromatin structure (i.e., DNA damage response, transcriptional regulation, and insulator function), are described. A potential cross talk between nuclear ADP-ribosylation processes and other NAD⁺-dependent pathways is discussed.

These authors contributed equally to this work.

This article has been cited by other articles:

• Olabisi, O. A., Soto-Nieves, N., Nieves, E., Yang, T. T. C., Yang, X., Yu, R. Y. L., Suk, H. Y., Macian, F., Chow, C.-W. (2008). Regulation of Transcription Factor NFAT by ADP-Ribosylation. Mol. Cell. Biol. 28: 2860-2871 [Abstract] [Full Text]  
• Luk, T., Malam, Z., Marshall, J. C. (2008). Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity. J. Leukoc. Biol. 83: 804-816 [Abstract] [Full Text]  
• von Lukowicz, T., Hassa, P. O., Lohmann, C., Boren, J., Braunersreuther, V., Mach, F., Odermatt, B., Gersbach, M., Camici, G. G., Stahli, B. E., Tanner, F. C., Hottiger, M. O., Luscher, T. F., Matter, C. M. (2008). PARP1 is required for adhesion molecule expression in atherogenesis. Cardiovasc Res 78: 158-166 [Abstract] [Full Text]  
• Sauve, A. A. (2008). NAD+ and Vitamin B3: From Metabolism to Therapies. J. Pharmacol. Exp. Ther. 324: 883-893 [Abstract] [Full Text]  
• Elser, M., Borsig, L., Hassa, P. O., Erener, S., Messner, S., Valovka, T., Keller, S., Gassmann, M., Hottiger, M. O. (2008). Poly(ADP-Ribose) Polymerase 1 Promotes Tumor Cell Survival by Coactivating Hypoxia-Inducible Factor-1-Dependent Gene Expression. Mol Cancer Res 6: 282-290 [Abstract] [Full Text]  
• Niere, M., Kernstock, S., Koch-Nolte, F., Ziegler, M. (2008). Functional Localization of Two Poly(ADP-Ribose)-Degrading Enzymes to the Mitochondrial Matrix. Mol. Cell. Biol. 28: 814-824 [Abstract] [Full Text]  
• Tramontano, F., Malanga, M., Quesada, P. (2007). Differential contribution of poly(ADP-ribose)polymerase-1 and -2 (PARP-1 and -2) to the poly(ADP-ribosyl)ation reaction in rat primary spermatocytes. Mol Hum Reprod 13: 821-828 [Abstract] [Full Text]  
• Moubarak, R. S., Yuste, V. J., Artus, C., Bouharrour, A., Greer, P. A., Menissier-de Murcia, J., Susin, S. A. (2007). Sequential Activation of Poly(ADP-Ribose) Polymerase 1, Calpains, and Bax Is Essential in Apoptosis-Inducing Factor-Mediated Programmed Necrosis. Mol. Cell. Biol. 27: 4844-4862 [Abstract] [Full Text]  
• Nusinow, D. A., Hernandez-Munoz, I., Fazzio, T. G., Shah, G. M., Kraus, W. L., Panning, B. (2007). Poly(ADP-ribose) Polymerase 1 Is Inhibited by a Histone H2A Variant, MacroH2A, and Contributes to Silencing of the Inactive X Chromosome. J. Biol. Chem. 282: 12851-12859 [Abstract] [Full Text]