This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Google Scholar
Google Scholar
Right arrow Articles by Seidel, J. J.
Right arrow Articles by Blackburn, E. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seidel, J. J.
Right arrow Articles by Blackburn, E. H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2008, p. 5736-5746, Vol. 28, No. 18
0270-7306/08/$08.00+0     doi:10.1128/MCB.00326-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Novel Tel1/ATM N-Terminal Motif, TAN, Is Essential for Telomere Length Maintenance and a DNA Damage Response{triangledown} ,{dagger}

Jeffrey J. Seidel, Carol M. Anderson, and Elizabeth H. Blackburn*

Department of Biochemistry and Biophysics, 600 16th Street, Room S316, University of California, San Francisco, San Francisco, California 94158

Received 26 February 2008/ Returned for modification 15 April 2008/ Accepted 16 June 2008

Tel1/ATM, a conserved phosphatidylinositol 3-kinase-related kinase (PIKK), acts in the response to DNA damage and regulates telomere maintenance. PIKK family members share an extended N-terminal region of low sequence homology. Sequence alignment of the N terminus of Tel1/ATM orthologs revealed a conserved, novel motif we term TAN (for Tel1/ATM N-terminal motif). Point mutations in conserved residues of the TAN motif resulted in telomere shortening, and its deletion caused the same short telomere phenotype as complete deletion of Tel1 did. Overexpressing Tel1 TAN mutants did not rescue telomere shortening. The TAN motif was also essential for the function of Tel1 in the response to DNA damage, as TAN-deleted Tel1 was indistinguishable from the complete lack of Tel1 in causing reduced viability and signaling through Rad53 upon DNA damage. Strikingly, TAN deletion reduced recruitment of Tel1 to a double-strand DNA break. Together, these results define a conserved sequence motif within an otherwise poorly defined region of the Tel1/ATM kinase family proteins that is essential for normal Tel1 function in Saccharomyces cerevisiae.

* Corresponding author. Mailing address: Department of Biochemistry and Biophysics, 600 16th Street, Room S316, University of California, San Francisco, San Francisco, CA 94158-2517. Phone: (415) 476-2824. Fax: (415) 514-2913. E-mail: Elizabeth.Blackburn{at}ucsf.edu

{triangledown} Published ahead of print on 14 July 2008.

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

Molecular and Cellular Biology, September 2008, p. 5736-5746, Vol. 28, No. 18
0270-7306/08/$08.00+0     doi:10.1128/MCB.00326-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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