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TORC1 inactivation induces a noncanonical, separase-independent cohesin degradation

Chihiro Yamada1, Honoka Goto2, Ayana Futaguchi2

  • 1Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan.

Bioscience, Biotechnology, and Biochemistry
|June 26, 2026
PubMed

Insights

Nutrient stress inactivates TORC1, causing proteasome-dependent cohesin degradation via a novel pathway. This bypasses securin and separase, revealing a second route to sister chromatid dissociation.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Target of rapamycin complex 1 (TORC1) links nutrient availability to cell growth.
  • TORC1 inactivation typically causes mitotic slippage through APC/C-Cdh1-mediated securin degradation and separase activation.
  • The precise mechanisms of cohesion loss during nutrient stress are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying cohesin loss upon TORC1 inactivation in budding yeast.
  • To identify novel pathways involved in sister chromatid dissociation during nutrient stress.

Main Methods:

  • Investigated cohesin degradation in budding yeast following TORC1 inactivation.
  • Utilized separase-resistant mutants and impaired APC/C conditions.
  • Analyzed proteasome-dependent degradation pathways.

Main Results:

  • TORC1 inactivation triggers proteasome-dependent cohesin degradation independent of securin and separase.
  • Separase itself is destabilized, but Scc1 degradation continues in separase-resistant mutants.
  • Cohesin degrades even when the Anaphase-Promoting Complex/Cyclosome (APC/C) is inhibited, suggesting an atypical ubiquitin ligase involvement.

Conclusions:

  • TORC1 inactivation initiates a noncanonical pathway for cohesin degradation.
  • This pathway operates in parallel to the known APC/C-Cdh1 pathway, representing a distinct mechanism for sister chromatid dissociation.
  • Unconventional degradation of mitotic factors contributes to aberrant cell division under nutrient stress.
Keywords:
cohesinsecurinseparasespindle assembly checkpoint (SAC)target of rapamycin complex 1 (TORC1)

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