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Updated: May 11, 2026
Examination of Mitotic and Meiotic Fission Yeast Nuclear Dynamics by Fluorescence Live-cell Microscopy
Published on: June 24, 2019
TORC2 is required to maintain genome stability during S phase in fission yeast
Miriam Schonbrun1, Masha Kolesnikov, Martin Kupiec
1Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel.
Abstract:
DNA damage can occur due to environmental insults or intrinsic metabolic processes and is a major threat to genome stability. The DNA damage response is composed of a series of well coordinated cellular processes that include activation of the DNA damage checkpoint, transient cell cycle arrest, DNA damage repair, and reentry into the cell cycle. Here we demonstrate that mutant cells defective for TOR complex 2 (TORC2) or the downstream AGC-like kinase, Gad8, are highly sensitive to chronic replication stress but are insensitive to ionizing radiation. We show that in response to replication stress, TORC2 is dispensable for Chk1-mediated cell cycle arrest but is required for the return to cell cycle progression. Rad52 is a DNA repair and recombination protein that forms foci at DNA damage sites and stalled replication forks. TORC2 mutant cells show increased spontaneous nuclear Rad52 foci, particularly during S phase, suggesting that TORC2 protects cells from DNA damage that occurs during normal DNA replication. Consistently, the viability of TORC2-Gad8 mutant cells is dependent on the presence of the homologous recombination pathway and other proteins that are required for replication restart following fork replication stalling. Our findings indicate that TORC2 is required for genome integrity. This may be relevant for the growing amount of evidence implicating TORC2 in cancer development.
Insights
Mutant cells lacking TOR complex 2 (TORC2) show increased DNA damage during replication. TORC2 is essential for cell cycle progression after replication stress, maintaining genome integrity.
Area of Science:
- Cellular biology
- Molecular genetics
- Cancer research
Background:
- DNA damage poses a significant threat to genome stability, triggering a complex DNA damage response.
- The DNA damage response involves cell cycle arrest, DNA repair, and cell cycle reentry.
- TOR complex 2 (TORC2) is implicated in various cellular processes, but its role in genome integrity is not fully understood.
Purpose of the Study:
- To investigate the role of TOR complex 2 (TORC2) in maintaining genome stability under replication stress.
- To determine the specific functions of TORC2 in DNA damage response pathways.
Main Methods:
- Utilized mutant cells deficient in TOR complex 2 (TORC2) or its downstream kinase Gad8.
- Assessed sensitivity to chronic replication stress and ionizing radiation.
- Analyzed Chk1-mediated cell cycle arrest and progression.
- Quantified spontaneous nuclear Rad52 foci formation.
- Evaluated the dependence on homologous recombination and replication restart pathways.
Main Results:
- TORC2-deficient cells exhibit high sensitivity to chronic replication stress but not ionizing radiation.
- TORC2 is dispensable for Chk1-mediated cell cycle arrest but crucial for cell cycle reentry post-replication stress.
- TORC2 mutant cells display increased spontaneous Rad52 foci during S phase, indicating DNA damage during replication.
- Cell viability in TORC2-Gad8 mutants depends on homologous recombination and replication restart mechanisms.
Conclusions:
- TOR complex 2 (TORC2) plays a critical role in maintaining genome integrity, particularly under replication stress.
- TORC2 is essential for timely replication restart and preventing DNA damage during normal DNA replication.
- The findings suggest a potential link between TORC2 dysfunction and cancer development.
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