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Molecular and Cellular Biology, September 2009, p. 5193-5202, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.01896-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Kinase-Independent Functions of TEL1 in Telomere Maintenance{triangledown} ,{dagger}

Yunmei Ma and Carol W. Greider*

Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Received 15 December 2008/ Returned for modification 16 January 2009/ Accepted 6 July 2009

TEL1 is important in Saccharomyces cerevisiae telomere maintenance, and its kinase activity is required. Tel1p associates with telomeres in vivo, is enriched at short telomeres, and enhances the binding of telomerase components to short telomeres. However, it is unclear how the kinase activity and telomere association contribute to Tel1p's overall function in telomere length maintenance. To investigate this question, we generated a set of single point mutants and a double point mutant (tel1KD) of Tel1p that were kinase deficient and two Xrs2p mutants that failed to bind Tel1p. Using these separation-of-function alleles in a de novo telomere elongation assay, we found, surprisingly, that the tel1KD allele and xrs2 C-terminal mutants were both partially functional. Combining the tel1KD and xrs2 C-terminal mutants had an additive effect and resembled the TEL1 null (tel1{Delta}) phenotype. These data indicate that Tel1p has two separate functions in telomere maintenance and that the Xrs2p-dependent recruitment of Tel1p to telomeres plays an important role even in the absence of its kinase activity.

* Corresponding author. Mailing address: Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 603 PCTB, 725 N. Wolfe Street, Baltimore, MD 21205. Phone: (410) 614-6506. Fax: (410) 614-2987. E-mail: cgreider{at}jhmi.edu

{triangledown} Published ahead of print on 13 July 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, September 2009, p. 5193-5202, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.01896-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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