TORC1 signaling regulates DNA replication via DNA replication protein levels

Kaori Yamamoto, Nishiho Makino, Masayoshi Nagai, Yoshimi Honma, Hiroyuki Araki, Takashi Ushimaru

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1128-1133
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume505
Issue number4
DOIs
Publication statusPublished - Nov 10 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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