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Published online before print March 11, 2008, 10.1101/gad.1646208
GENES & DEVELOPMENT 22:854-859, 2008
©2008 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH COMMUNICATION

Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break

Carol M. Anderson1, Dmitry Korkin2,3,4,5, Dana L. Smith1, Svetlana Makovets1, Jeffrey J. Seidel1, Andrej Sali2,3,4, and Elizabeth H. Blackburn1,6

1 Department of Biochemistry, University of California, San Francisco, California 94143, USA; 2 Department of Biopharmaceutical Sciences, University of California, San Francisco, California 94143, USA; 3 Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, USA; 4 California Institute for Quantitative Biomedical Research, University of California, San Francisco, California 94143, USA

The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.

[Keywords: DNA damage signaling; checkpoint; Clk-2; PI3 kinase-like kinase; {alpha}-superhelical protein; telomere]]

Received December 21, 2007; revised version accepted February 11, 2008.

5 Present address: Informatics Institute and Department of Computer Science, University of Missouri, Columbia, MO 65211, USA.

6 Corresponding author.

E-MAIL elizabeth.blackburn{at}ucsf.edu; FAX (415) 514-2913.

Supplemental material is available at http://www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1646208.


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