Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo.
The phosphoinositide (PI)-3-kinase-related kinase (PIKK) family proteins Tel1p and Mec1p have been implicated in the telomere integrity of Saccharomyces cerevisiae. However, the mechanism of PIKK-mediated telomere length control remains unclear. Here, we show that Tel1p and Mec1p are recruited to the telomeres at specific times in the cell cycle in a mutually exclusive manner. In particular, Mec1p interacts with the telomeres during late S phase and is associated preferentially with shortened telomeres. We propose a model in which telomere integrity is maintained by the reciprocal association of PIKKs, and Mec1p acts as a sensor for structural abnormalities in the telomeres. Our study suggests a mechanistic similarity between telomere length regulation and DNA double-strand break repair, both of which are achieved by the direct association of PIKKs.
Takata
Hideki
H
Department of Geriatric Research, National Institute for Longevity Sciences, Obu, Aichi 474-8522, Japan.
Kanoh
Yutaka
Y
Gunge
Norio
N
Shirahige
Katsuhiko
K
Matsuura
Akira
A
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D004247:DNA; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; C091561:ATM1 protein, S cerevisiae; C088937:MEC1 protein, S cerevisiae; C513623:TEL1 protein, S cerevisiae