Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break.
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.
Anderson
Carol M
CM
Department of Biochemistry, University of California, San Francisco, California 94143, USA.
Korkin
Dmitry
D
Smith
Dana L
DL
Makovets
Svetlana
S
Seidel
Jeffrey J
JJ
Sali
Andrej
A
Blackburn
Elizabeth H
EH
D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004789:Enzyme Activation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C444420:Tel2 protein, S cerevisiae; D034501:Telomere-Binding Proteins; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae