TY - JOUR
T1 - TORC1 signaling regulates DNA replication via DNA replication protein levels
AU - Yamamoto, Kaori
AU - Makino, Nishiho
AU - Nagai, Masayoshi
AU - Honma, Yoshimi
AU - Araki, Hiroyuki
AU - Ushimaru, Takashi
N1 - Funding Information:
We thank Bruce Stillman, Daniel Klionsky, Erin O'Shea, Kim Arndt, Michael Hall, Stephen Elledge, Tsutomu Kishi, and Uttam Surana for generous gifts of materials, and Masahiro Uritani, Ayumu Yamamoto, and laboratory members of TU for helpful discussions. This work was supported in part by the Japan Society for the Promotion of Science (JSPS) (grant No. 16657049 , 18657055 , 19370082 , 23570225 , and 18K06212 to TU) and NIG Cooperative Research Program (grant No. 2004-B2 and 2005-B1 to TU).
Funding Information:
We thank Bruce Stillman, Daniel Klionsky, Erin O'Shea, Kim Arndt, Michael Hall, Stephen Elledge, Tsutomu Kishi, and Uttam Surana for generous gifts of materials, and Masahiro Uritani, Ayumu Yamamoto, and laboratory members of TU for helpful discussions. This work was supported in part by the Japan Society for the Promotion of Science (JSPS) (grant No. 16657049, 18657055, 19370082, 23570225, and 18K06212 to TU) and NIG Cooperative Research Program (grant No. 2004-B2 and 2005-B1 to TU).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11/10
Y1 - 2018/11/10
N2 - Accurate DNA replication is at the heart of faithful genome transmission in dividing cells. DNA replication is strictly controlled by various factors. However, how environmental stresses such as nutrient starvation impact on these factors and DNA replication is largely unknown. Here we show that DNA replication is regulated by target of rapamycin complex 1 (TORC1) protein kinase, which is a central regulator of cell growth and proliferation in response to nutrients. TORC1 inactivation reduced the levels of various proteins critical for DNA replication initiation, such as Mcm3, Orc3, Cdt1, and Sld2, and retarded DNA replication. TORC1 inactivation promoted proteasome-mediated Mcm3 degradation. Skp1–Cullin–F-box (SCF)-Grr1 and PEST motif mediated Mcm3 degradation. TORC1-downstream factors PP2A-Cdc55 protein phosphatase and protein kinase A regulated Mcm3 degradation. This study showed that TORC1 signaling modulates DNA replication to coordinate cell growth and genome replication in response to nutrient availability.
AB - Accurate DNA replication is at the heart of faithful genome transmission in dividing cells. DNA replication is strictly controlled by various factors. However, how environmental stresses such as nutrient starvation impact on these factors and DNA replication is largely unknown. Here we show that DNA replication is regulated by target of rapamycin complex 1 (TORC1) protein kinase, which is a central regulator of cell growth and proliferation in response to nutrients. TORC1 inactivation reduced the levels of various proteins critical for DNA replication initiation, such as Mcm3, Orc3, Cdt1, and Sld2, and retarded DNA replication. TORC1 inactivation promoted proteasome-mediated Mcm3 degradation. Skp1–Cullin–F-box (SCF)-Grr1 and PEST motif mediated Mcm3 degradation. TORC1-downstream factors PP2A-Cdc55 protein phosphatase and protein kinase A regulated Mcm3 degradation. This study showed that TORC1 signaling modulates DNA replication to coordinate cell growth and genome replication in response to nutrient availability.
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U2 - 10.1016/j.bbrc.2018.10.018
DO - 10.1016/j.bbrc.2018.10.018
M3 - Article
C2 - 30316513
AN - SCOPUS:85054572030
SN - 0006-291X
VL - 505
SP - 1128
EP - 1133
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -