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Putting the brake on FEAR: Tof2 promotes the biphasic release of Cdc14 phosphatase during mitotic exit

William G Waples1, Charly Chahwan, Marta Ciechonska

  • 1Department of Molecular Genetics, University of Toronto, ON, Canada.

Molecular Biology of the Cell
|October 17, 2008
PubMed

Insights

Tof2 restrains Cdc14 phosphatase release from the nucleolus during anaphase, ensuring proper chromosome segregation. This regulation is crucial for coordinating the biphasic release of Cdc14, essential for cell division.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Chromosome segregation requires rDNA array hypercondensation, dependent on condensin and Cdc14 phosphatase.
  • Understanding the regulation of rDNA condensation and Cdc14 phosphatase activity is crucial for cell cycle progression.

Purpose of the Study:

  • To identify novel genetic interactions involved in budding yeast condensin function.
  • To elucidate the role of specific genes, including TOF2, in rDNA condensation and chromosome segregation.
  • To understand the regulatory mechanism of Cdc14 phosphatase release during anaphase.

Main Methods:

  • Systematic genetic screens to identify interactions with budding yeast condensin.
  • Analysis of gene deletion mutants (e.g., tof2Δ) to assess their role in rDNA condensation.
  • Investigation of protein interactions and localization (e.g., Cdc14 release from the nucleolus).

Main Results:

  • Identified FOB1, CSM1, LRS4, and TOF2 as essential for mitotic rDNA condensation.
  • Demonstrated that Tof2, unlike Fob1, Csm1, and Lrs4, is specifically required during anaphase.
  • Showed that Tof2 interacts with Cdc14 phosphatase and its absence enhances Cdc14 release, even when the mitotic exit network (MEN) is compromised.

Conclusions:

  • Tof2 plays a critical role in coordinating the biphasic release of Cdc14 phosphatase during anaphase.
  • Tof2 restrains Cdc14 in the nucleolus after FEAR network activation, allowing for subsequent MEN-mediated release.
  • This regulation by Tof2 is vital for timely and accurate chromosome segregation.

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