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A comprehensive model to predict mitotic division in budding yeasts.

Sabyasachi Sutradhar1, Vikas Yadav2, Shreyas Sridhar2

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A computational model reveals biased nucleation of cytoplasmic microtubules is key for directional nuclear migration during yeast cell division. Distinct pathways in budding yeasts highlight microtubule dynamics essential for chromosome segregation.

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Area of Science:

  • Cell Biology
  • Systems Biology
  • Computational Biology

Background:

  • High-fidelity chromosome segregation is crucial for cell division.
  • Mitotic events involve complex, interdependent interactions.
  • Budding yeasts (Ascomycota and Basidiomycota) serve as model organisms.

Purpose of the Study:

  • To develop a minimal computational model of mitotic events in budding yeasts.
  • To comprehend the interdependence of cellular processes during mitosis.
  • To identify key factors driving chromosome segregation, spindle alignment, and nuclear migration.

Main Methods:

  • Systems biology approach to model construction.
  • Development of a minimal computational model.
  • Validation against experimental observations of spindle alignment, nuclear migration, and microtubule dynamics.

Main Results:

  • The model accurately reproduces experimental data for yeast cell division.
  • Biased nucleation of cytoplasmic microtubules (cMTs) is identified as essential for directional nuclear migration.
  • Two distinct pathways involving cMTs and cortical dyneins differentiate nuclear migration and spindle orientation between fungal phyla.
  • The model predicts the roles of specific microtubule classes in chromosome segregation.

Conclusions:

  • Biased cytoplasmic microtubule nucleation is a critical determinant of directional nuclear migration.
  • Divergent molecular pathways govern nuclear migration and spindle orientation in Ascomycota and Basidiomycota.
  • The developed model provides a versatile tool for simulating perturbations in mitotic cell division.