TY - JOUR
T1 - TOR regulates cell death induced by telomere dysfunction in budding yeast
AU - Qi, Haiyan
AU - Chen, Yongjie
AU - Fu, Xuan
AU - Lin, Chao Po
AU - Zheng, X. F.Steven
AU - Liu, Leroy F.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/10/24
Y1 - 2008/10/24
N2 - Telomere dysfunction is known to induce growth arrest (senescence) and cell death. However, the regulation of the senescence-death process is poorly understood. Here using a yeast dysfunctional telomere model cdc13-1, which carries a temperature sensitive-mutant telomere binding protein Cdc13p, we demonstrate that inhibition of TOR (Target of Rapamycin), a central regulator of nutrient pathways for cell growth, prevents cell death, but not growth arrest, induced by inactivation of Cdc13-1p. This function of TOR is novel and separable from its G1 inhibition function, and not associated with alterations in the telomere length, the amount of G-tails, and the telomere position effect (TPE) in cdc13-1 cells. Furthermore, antioxidants were also shown to prevent cell death initiated by inactivation of cdc13-1. Moreover, inhibition of TOR was also shown to prevent cell death induced by inactivation of telomerase in an est1 mutant. Interestingly, rapamycin did not prevent cell death induced by DNA damaging agents such as etoposide and UV. In the aggregate, our results suggest that the TOR signaling pathway is specifically involved in the regulation of cell death initiated by telomere dysfunction.
AB - Telomere dysfunction is known to induce growth arrest (senescence) and cell death. However, the regulation of the senescence-death process is poorly understood. Here using a yeast dysfunctional telomere model cdc13-1, which carries a temperature sensitive-mutant telomere binding protein Cdc13p, we demonstrate that inhibition of TOR (Target of Rapamycin), a central regulator of nutrient pathways for cell growth, prevents cell death, but not growth arrest, induced by inactivation of Cdc13-1p. This function of TOR is novel and separable from its G1 inhibition function, and not associated with alterations in the telomere length, the amount of G-tails, and the telomere position effect (TPE) in cdc13-1 cells. Furthermore, antioxidants were also shown to prevent cell death initiated by inactivation of cdc13-1. Moreover, inhibition of TOR was also shown to prevent cell death induced by inactivation of telomerase in an est1 mutant. Interestingly, rapamycin did not prevent cell death induced by DNA damaging agents such as etoposide and UV. In the aggregate, our results suggest that the TOR signaling pathway is specifically involved in the regulation of cell death initiated by telomere dysfunction.
UR - http://www.scopus.com/inward/record.url?scp=55849125436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55849125436&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0003520
DO - 10.1371/journal.pone.0003520
M3 - Article
C2 - 18949037
AN - SCOPUS:55849125436
SN - 1932-6203
VL - 3
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e3520
ER -