TORC1, Tel1/Mec1, and Mpk1 regulate autophagy induction after DNA damage in budding yeast

Sayuri Ueda; Ryota Ozaki; Atsuki Kaneko; Ryoma Akizuki; Haruko Katsuta; Atsuhiro Miura; Akira Matsuura; Takashi Ushimaru

doi:10.1016/j.cellsig.2019.109344

TORC1, Tel1/Mec1, and Mpk1 regulate autophagy induction after DNA damage in budding yeast

Cell Signal. 2019 Oct:62:109344. doi: 10.1016/j.cellsig.2019.109344. Epub 2019 Jun 12.

Authors

Sayuri Ueda¹, Ryota Ozaki², Atsuki Kaneko², Ryoma Akizuki², Haruko Katsuta¹, Atsuhiro Miura³, Akira Matsuura³, Takashi Ushimaru⁴

Affiliations

¹ Department of Bioscience, Faculty of Science, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan.
² Course of Biological Science, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan.
³ Department of Biology, Graduate School of Science, Chiba University, Inage-ku, Chiba 263-8522, Japan.
⁴ Department of Bioscience, Faculty of Science, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan; Course of Biological Science, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka 422-8021, Japan. Electronic address: ushimaru.takashi@shizuoka.ac.jp.

PMID: 31201849
DOI: 10.1016/j.cellsig.2019.109344

Abstract

Target of rapamycin complex 1 (TORC1) protein kinase responds to various stresses including genotoxic stress. However, its molecular mechanism is poorly understood. Here, we show that DNA damage induces nonselective and selective autophagy in budding yeast. DNA damage caused the attenuation of TORC1 activity, dephosphorylation of Atg13, and autophagy induction. The TORC1-upstream Rag GTPase Gtr1 was not required for TORC1 inactivation and autophagy induction after DNA damage. Furthermore, DNA damage responsive protein kinases Mec1/ATM and Tel1/ATR, and stress-responsive mitogen-activated protein kinase Mpk1/Slt2 were required for the full induction of autophagy. Autophagic proteolysis was required for DNA damage tolerance in TORC1 inactive conditions. This study revealed that multiple protein kinases regulate DNA damage-induced autophagy.

Keywords: Autophagy; DNA damage; Mec1; Mpk1; TORC1; Tel1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Autophagy / genetics*
Autophagy-Related Proteins / genetics
DNA Damage / genetics
Gene Expression Regulation, Developmental
Gene Expression Regulation, Fungal / genetics
Intracellular Signaling Peptides and Proteins / genetics*
Mechanistic Target of Rapamycin Complex 1 / genetics
Mitogen-Activated Protein Kinases / genetics*
Monomeric GTP-Binding Proteins / genetics
Protein Serine-Threonine Kinases / genetics*
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae Proteins / genetics*
Signal Transduction / genetics

Substances

ATG13 protein, S cerevisiae
Adaptor Proteins, Signal Transducing
Autophagy-Related Proteins
Gtr1 protein, S cerevisiae
Intracellular Signaling Peptides and Proteins
Saccharomyces cerevisiae Proteins
MEC1 protein, S cerevisiae
Mechanistic Target of Rapamycin Complex 1
Protein Serine-Threonine Kinases
TEL1 protein, S cerevisiae
Mitogen-Activated Protein Kinases
SLT2 protein, S cerevisiae
Monomeric GTP-Binding Proteins