TORC2-a new player in genome stability

Ronit Weisman1, Adiel Cohen2, Susan M Gasser3

  • 1Department of Natural and Life Sciences, The Open University of Israel, Raanana, Israel ronitwe@openu.ac.il susan.gasser@fmi.ch.

Insights

The target of rapamycin complex 2 (TORC2) plays a key role in DNA damage survival, a finding with potential implications for cancer chemotherapy. This research highlights TORC2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The mechanistic target of rapamycin (mTOR) pathway, particularly mTOR complex 1 (TORC1), is extensively studied in metabolic and cancer research.
  • TORC1 is the canonical target of rapamycin and is involved in regulating autophagy, protein synthesis, and cell growth.
  • TORC2, a less-studied complex, is emerging as crucial for cellular responses.

Purpose of the Study:

  • To investigate the role of TORC2 in DNA damage survival.
  • To explore the conserved function of TORC2 in different yeast species.
  • To assess the potential of targeting mTORC2 in human cancer chemotherapy.

Main Methods:

  • Comparative studies in budding and fission yeast species.
  • Analysis of TORC2's downstream effectors, including AGC kinases.
  • Investigating the link between TORC2, lipid biosynthesis, actin cytoskeleton, and DNA damage response.
  • Preliminary modulation studies in human cancer cells.

Main Results:

  • TORC2 has a conserved role in DNA damage survival across yeast species.
  • TORC2 regulates lipid biosynthesis and the actin cytoskeleton via AGC kinases.
  • These downstream pathways are surprisingly implicated in oxidative DNA damage survival.
  • Early data suggest mTORC2 modulation may enhance chemotherapy efficacy in cancer cells.

Conclusions:

  • TORC2 is a critical regulator of DNA damage survival, extending beyond its known roles.
  • The downstream targets of TORC2, particularly AGC kinases, are involved in DNA repair mechanisms.
  • Targeting mTORC2 presents a promising avenue for novel cancer therapeutic strategies.

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