4.6 Article

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

Journal

CELLULAR SIGNALLING
Volume 62, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2019.109344

Keywords

Autophagy; DNA damage; Mec1; Mpk1; Tel1; TORC1

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Funding

  1. Japan Society for the Promotion of Science (JSPS) [23570225, 18K06212]
  2. Grants-in-Aid for Scientific Research [18K06212] Funding Source: KAKEN

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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 Gtrl 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.

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