title: Tor complex 1 controls telomere length by affecting the level of Ku.
abstract: Telomeres are specialized DNA-protein structures at the ends of eukaryotic chromosomes. Telomeric DNA is synthesized by telomerase, which is expressed only at the early stages of development [1, 2]. To become malignant, any cell has to be able to replenish telomeres [3]. Thus, understanding how telomere length is monitored has significant medical implications, especially in the fields of aging and cancer. In yeast, telomerase is constitutively active. A large network of genes participates in controlling telomere length [4-8]. Tor1 and Tor2 (targets of rapamycin [9]) are two similar kinases that regulate cell growth [10]. Both can be found as part of the TOR complex 1 (TORC1 [11]), which coordinates the response to nutrient starvation and is sensitive to rapamycin [12]. The rapamycin-insensitive TOR complex 2 (TORC2) contains only Tor2 and regulates actin cytoskeleton polarization [13]. Here we provide evidence for a role of TORC1 in telomere shortening upon starvation in yeast cells. The TORC1 signal is transduced by the Gln3/Gat1/Ure2 pathway, which controls the levels of the Ku heterodimer, a telomere regulator. We discuss the potential implications for the usage of rapamycin as a therapeutic agent against cancer and the effect that calorie restriction may have on telomere length.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Ungar
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Harari
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
authors.forename: Martin
authors.initials: M
authors.lastname: Kupiec
mesh_terms: D031204:Caloric Restriction; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D011328:Prions / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D013045:Species Specificity; D016615:Telomere / Q000378:metabolism*; D059506:Telomere Shortening; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C096100:GAT1 protein, S cerevisiae; D050980:GATA Transcription Factors; C071664:GLN3 protein, S cerevisiae; C082119:NGR1 protein, S cerevisiae; D011328:Prions; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; C081647:high affinity DNA-binding factor, S cerevisiae; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D020123:Sirolimus