This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cortes, U.
Right arrow Articles by Wang, Z.-Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cortes, U.
Right arrow Articles by Wang, Z.-Q.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2004, p. 7163-7178, Vol. 24, No. 16
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.16.7163-7178.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Depletion of the 110-Kilodalton Isoform of Poly(ADP-Ribose) Glycohydrolase Increases Sensitivity to Genotoxic and Endotoxic Stress in Mice

Ulrich Cortes,1 Wei-Min Tong,1 Donna L. Coyle,2 Mirella L. Meyer-Ficca,2 Ralph G. Meyer,2 Virginie Petrilli,1 Zdenko Herceg,1 Elaine L. Jacobson,2 Myron K. Jacobson,2 and Zhao-Qi Wang1*

International Agency for Research on Cancer, 69008 Lyon, France,1 Department of Pharmacology and Toxicology, College of Pharmacy, and Arizona Cancer Center, University of Arizona, Tucson, Arizona 857242

Received 12 March 2004/ Returned for modification 22 April 2004/ Accepted 14 May 2004

Poly(ADP-ribosylation) is rapidly stimulated in cells following DNA damage. This posttranslational modification is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG). Although the role of PARP-1 in response to DNA damage has been studied extensively, the function of PARG and the impact of poly(ADP-ribose) homeostasis in various cellular processes are largely unknown. Here we show that by gene targeting in embryonic stem cells and mice, we specifically deleted the 110-kDa PARG protein (PARG110) normally found in the nucleus and that depletion of PARG110 severely compromised the automodification of PARP-1 in vivo. PARG110-deficient mice were viable and fertile, but these mice were hypersensitive to alkylating agents and ionizing radiation. In addition, these mice were susceptible to streptozotocin-induced diabetes and endotoxic shock. These data indicate that PARG110 plays an important role in DNA damage responses and in pathological processes.

* Corresponding author. Mailing address: International Agency for Research on Cancer, 150 cours Albert-Thomas, 69008 Lyon, France. Phone: 33-4-72-73-8510. Fax: 33-4-72-73-8329. E-mail: zqwang{at}iarc.fr.

Molecular and Cellular Biology, August 2004, p. 7163-7178, Vol. 24, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.16.7163-7178.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Erdelyi, K., Bai, P., Kovacs, I., Szabo, E., Mocsar, G., Kakuk, A., Szabo, C., Gergely, P., Virag, L. (2009). Dual role of poly(ADP-ribose) glycohydrolase in the regulation of cell death in oxidatively stressed A549 cells. FASEB J. 23: 3553-3563 [Abstract] [Full Text]  
  • Meyer-Ficca, M. L., Lonchar, J., Credidio, C., Ihara, M., Li, Y., Wang, Z.-Q., Meyer, R. G. (2009). Disruption of Poly(ADP-Ribose) Homeostasis Affects Spermiogenesis and Sperm Chromatin Integrity in Mice. Biol. Reprod. 81: 46-55 [Abstract] [Full Text]  
  • Formentini, L., Macchiarulo, A., Cipriani, G., Camaioni, E., Rapizzi, E., Pellicciari, R., Moroni, F., Chiarugi, A. (2009). Poly(ADP-ribose) Catabolism Triggers AMP-dependent Mitochondrial Energy Failure. J. Biol. Chem. 284: 17668-17676 [Abstract] [Full Text]  
  • Ame, J.-C., Fouquerel, E., Gauthier, L. R., Biard, D., Boussin, F. D., Dantzer, F., de Murcia, G., Schreiber, V. (2009). Radiation-induced mitotic catastrophe in PARG-deficient cells. J. Cell Sci. 122: 1990-2002 [Abstract] [Full Text]  
  • Uchiumi, F., Sakakibara, G., Sato, J., Tanuma, S.-i. (2008). Characterization of the promoter region of the human PARG gene and its response to PU.1 during differentiation of HL-60 cells.. GENES CELLS 13: 1229-1247 [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]  
  • Fisher, A. E. O., Hochegger, H., Takeda, S., Caldecott, K. W. (2007). Poly(ADP-Ribose) Polymerase 1 Accelerates Single-Strand Break Repair in Concert with Poly(ADP-Ribose) Glycohydrolase. Mol. Cell. Biol. 27: 5597-5605 [Abstract] [Full Text]  
  • Keil, C., Grobe, T., Li Oei, S. (2006). MNNG-induced Cell Death Is Controlled by Interactions between PARP-1, Poly(ADP-ribose) Glycohydrolase, and XRCC1. J. Biol. Chem. 281: 34394-34405 [Abstract] [Full Text]  
  • Hassa, P. O., Haenni, S. S., Elser, M., Hottiger, M. O. (2006). Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?. Microbiol. Mol. Biol. Rev. 70: 789-829 [Abstract] [Full Text]  
  • Kim, M. Y., Zhang, T., Kraus, W. L. (2005). Poly(ADP-ribosyl)ation by PARP-1: `PAR-laying' NAD+ into a nuclear signal. Genes Dev. 19: 1951-1967 [Abstract] [Full Text]  
  • Erdelyi, K., Kiss, A., Bakondi, E., Bai, P., Szabo, C., Gergely, P., Erdodi, F., Virag, L. (2005). Gallotannin Inhibits the Expression of Chemokines and Inflammatory Cytokines in A549 Cells. Mol. Pharmacol. 68: 895-904 [Abstract] [Full Text]  
  • Patel, N. S.A., Cortes, U., Di Poala, R., Mazzon, E., Mota-Filipe, H., Cuzzocrea, S., Wang, Z.-Q., Thiemermann, C. (2005). Mice Lacking the 110-kD Isoform of Poly(ADP-Ribose) Glycohydrolase Are Protected against Renal Ischemia/Reperfusion Injury. J. Am. Soc. Nephrol. 16: 712-719 [Abstract] [Full Text]  
  • Koh, D. W., Lawler, A. M., Poitras, M. F., Sasaki, M., Wattler, S., Nehls, M. C., Stoger, T., Poirier, G. G., Dawson, V. L., Dawson, T. M. (2004). Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. Proc. Natl. Acad. Sci. USA 101: 17699-17704 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»