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TORC2 coordinates MBF-dependent transcription and restrains oxidative stress responses during DNA replication stress

Adiel Cohen1, Ava Mouzon2, Uri Sprecher2

  • 1Department of Natural Sciences, The Open University of Israel, Ranana, Israel.

The Journal of Biological Chemistry
|February 6, 2026
PubMed

Insights

Target of Rapamycin Complex 2 (TORC2) ensures proper gene activation during replication stress by regulating RNA polymerase II. TORC2 also prevents unwanted oxidative stress responses in Schizosaccharomyces pombe.

Area of Science:

  • Cellular biology
  • Molecular genetics
  • Stress response pathways

Background:

  • Target of Rapamycin (TOR) kinase is crucial for growth, metabolism, and stress adaptation.
  • TOR Complex 2 (TORC2) in Schizosaccharomyces pombe is vital for survival under stress, including replication stress.
  • The MluI-binding factor (MBF) complex controls cell cycle progression and DNA replication stress responses.

Purpose of the Study:

  • To investigate the role of TORC2 in regulating gene transcription during replication stress.
  • To elucidate how TORC2 influences RNA polymerase II dynamics at MBF-dependent genes.
  • To determine if TORC2 impacts other stress response pathways, such as oxidative stress.

Main Methods:

  • Analysis of RNA polymerase II (Pol II) initiation and elongation forms at MBF promoters and coding regions.
  • Assessment of gene expression changes in TORC2-deficient cells under replication stress.
  • Measurement of reactive oxygen species (ROS) levels in TORC2 mutant cells.

Main Results:

  • TORC2 is essential for the accumulation of initiating Pol II at MBF promoters during replication stress.
  • TORC2 deficiency leads to aberrant accumulation of elongating Pol II in MBF gene bodies, impairing gene induction.
  • TORC2-mutant cells show inappropriate upregulation of oxidative stress genes and increased ROS levels under replication stress.

Conclusions:

  • TORC2 is critical for the precise regulation of MBF-dependent gene transcription during replication stress.
  • TORC2 acts to balance Pol II initiation and elongation, ensuring proper gene activation.
  • TORC2 plays a role in suppressing the activation of oxidative stress pathways, preventing ROS accumulation during replication stress.
Keywords:
DNA replication stressRNA pol IISchizosaccharomyces pombeTOR complexTORC2oxidative stresstranscription elongationtranscription initiation

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