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Molecular and Cellular Biology, July 2005, p. 5567-5578, Vol. 25, No. 13
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.13.5567-5578.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Distinct Requirements for Pot1 in Limiting Telomere Length and Maintaining Chromosome Stability

Jeremy T. Bunch,1 Nancy S. Bae,1 Jessica Leonardi,1 and Peter Baumann1,2*

Stowers Institute for Medical Research, Kansas City, Missouri 64110,1 Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, Kansas 661602

Received 15 February 2005/ Returned for modification 14 March 2005/ Accepted 30 March 2005

The fission yeast Pot1 (protection of telomeres) protein binds to the single-stranded extensions at the ends of telomeres, where its presence is critical for the maintenance of linear chromosomes. Homologs of Pot1 have been identified in a wide variety of eukaryotes, including plants, animals, and humans. We now show that Pot1 plays dual roles in telomere length regulation and chromosome end protection. Using a series of Pot1 truncation mutants, we have defined distinct areas of the protein required for chromosome stability and for limiting access to telomere ends by telomerase. We provide evidence that a large portion of Pot1, including the N-terminal DNA binding domain and amino acids close to the C terminus, is essential for its protective function. C-terminal Pot1 fragments were found to exert a dominant-negative effect by displacing endogenous Pot1 from telomeres. Reducing telomere-bound Pot1 in this manner resulted in dramatic lengthening of the telomere tract. Upon further reduction of Pot1 at telomeres, the opposite phenotype was observed: loss of telomeric DNA and chromosome end fusions. Our results demonstrate that cells must carefully regulate the amount of telomere-bound Pot1 to differentiate between allowing access to telomerase and catastrophic loss of telomeres.

* Corresponding author. Mailing address: Stowers Institute, 1000 E. 50th Street, Kansas City, MO 64110. Phone: (816) 926-4445. Fax: (816) 926-2096. E-mail: peb{at}stowers-institute.org.

Molecular and Cellular Biology, July 2005, p. 5567-5578, Vol. 25, No. 13
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.13.5567-5578.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Box, J. A., Bunch, J. T., Zappulla, D. C., Glynn, E. F., Baumann, P. (2008). A Flexible Template Boundary Element in the RNA Subunit of Fission Yeast Telomerase. J. Biol. Chem. 283: 24224-24233 [Abstract] [Full Text]  
  • Rossignol, P., Collier, S., Bush, M., Shaw, P., Doonan, J. H. (2007). Arabidopsis POT1A interacts with TERT-V(I8), an N-terminal splicing variant of telomerase. J. Cell Sci. 120: 3678-3687 [Abstract] [Full Text]  
  • Kibe, T., Ono, Y., Sato, K., Ueno, M. (2007). Fission Yeast Taz1 and RPA Are Synergistically Required to Prevent Rapid Telomere Loss. Mol. Biol. Cell 18: 2378-2387 [Abstract] [Full Text]  
  • Xhemalce, B., Riising, E. M., Baumann, P., Dejean, A., Arcangioli, B., Seeler, J.-S. (2007). Role of SUMO in the dynamics of telomere maintenance in fission yeast. Proc. Natl. Acad. Sci. USA 104: 893-898 [Abstract] [Full Text]  
  • Torigoe, H., Furukawa, A. (2007). Tetraplex Structure of Fission Yeast Telomeric DNA and Unfolding of the Tetraplex on the Interaction with Telomeric DNA Binding Protein Pot1. J Biochem 141: 57-68 [Abstract] [Full Text]  


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