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Updated: Apr 27, 2026

Genome-wide Surveillance of Transcription Errors in Eukaryotic Organisms
Published on: September 13, 2018
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.
Abstract:
The inhibition of the central growth regulatory kinase TOR, which participates in two complexes, TORC1 and TORC2, has been a focus of metabolic and cancer studies for many years. Most studies have dealt with TORC1, the canonical target of rapamycin, and the role of this complex in autophagy, protein synthesis, and cell growth control. Recent work on TORC2 in budding and fission yeast species points to a conserved role of this lesser-known TOR complex in the survival of DNA damage. In budding yeast, TORC2 controls lipid biosynthesis and actin cytoskeleton through downstream AGC kinases, which are now, surprisingly, implicated in the survival of oxidative DNA damage. Preliminary data from mTORC2 modulation in cancer cells suggest that an extension to human chemotherapy is worth exploring.
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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