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 Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chiang, Y. J. Articles by Hodes, R. J. Search for Related Content PubMed PubMed Citation Articles by Chiang, Y. J. Articles by Hodes, R. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2006, p. 2037-2043, Vol. 26, No. 6
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.6.2037-2043.2006

Generation and Characterization of Telomere Length Maintenance in Tankyrase 2-Deficient Mice

Y. Jeffrey Chiang,^1* My-Linh Nguyen,¹ Sujatha Gurunathan,¹ Patrick Kaminker,² Lino Tessarollo,³ Judith Campisi,² and Richard J. Hodes^1,4

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892,¹ Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720,² Center for Cancer Research, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21702,³ National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892⁴

Received 2 December 2005/ Accepted 21 December 2005

Telomere length and function are crucial factors that determine the capacity for cell proliferation and survival, mediate cellular senescence, and play a role in malignant transformation in eukaryotic systems. The telomere length of a specific mammalian species is maintained within a given range by the action of telomerase and telomere-associated proteins. TRF1 is a telomere-associated protein that inhibits telomere elongation by its binding to telomere repeats, preventing access to telomerase. Human TRF1 interacts with tankyrase 1 and tankyrase 2 proteins, two related members of the tankyrase family shown to have poly(ADP-ribose) polymerase activity. Human tankyrase 1 is reported to ADP-ribosylate TRF1 and to down-regulate the telomeric repeat binding activity of TRF1, resulting in telomerase-dependent telomere elongation. Human tankyrase 2 is proposed to have activity similar to that of tankyrase 1, although tankyrase 2 function has been less extensively characterized. In the present study, we have assessed the in vivo function of mouse tankyrase 2 by germ line gene inactivation and show that inactivation of tankyrase 2 does not result in detectable alteration in telomere length when monitored through multiple generations of breeding. This finding suggests that either mouse tankyrases 1 and 2 have redundant functions in telomere length maintenance or that mouse tankyrase 2 differs from human tankyrase 2 in its role in telomere length maintenance. Tankyrase 2 deficiency did result in a significant decrease in body weight sustained through at least the first year of life, most marked in male mice, suggesting that tankyrase 2 functions in potentially telomerase-independent pathways to affect overall development and/or metabolism.

---

* Corresponding author. Mailing address: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, 4B36, 9000 Rockville Pike, Bethesda, MD 20892. Phone: (301) 496-1376. Fax: (301) 496-0887. E-mail: chiangj{at}mail.nih.gov.

---

Molecular and Cellular Biology, March 2006, p. 2037-2043, Vol. 26, No. 6
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.6.2037-2043.2006

This article has been cited by other articles:

• Munoz, P., Blanco, R., de Carcer, G., Schoeftner, S., Benetti, R., Flores, J. M., Malumbres, M., Blasco, M. A. (2009). TRF1 Controls Telomere Length and Mitotic Fidelity in Epithelial Homeostasis. Mol. Cell. Biol. 29: 1608-1625 [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]