Ase1/Prc1-dependent spindle elongation corrects merotely during anaphase in fission yeast

Thibault Courtheoux1, Guillaume Gay, Yannick Gachet

  • 1Université de Toulouse, Laboratoire de Biologie Cellulaire et Moléculaire du Controle de la Prolifération UMR5088, F-31062 Toulouse, France.

Insights

Sister chromatid segregation relies on correct kinetochore-microtubule attachments. This study shows merotelic attachments are corrected by microtubule forces, preventing cell division errors.

Area of Science:

  • Cell Biology
  • Cytoskeletal Dynamics
  • Mitotic Regulation

Background:

  • Faithful chromosome segregation is crucial for cell division.
  • Merotelic kinetochore-microtubule attachment is a misattachment error where one kinetochore binds microtubules from both spindle poles.
  • This error can lead to aneuploidy and cell cycle defects.

Purpose of the Study:

  • To investigate the mechanisms underlying the correction of merotelic kinetochore-microtubule attachments.
  • To determine the role of microtubule forces and specific proteins in merotelic attachment resolution.
  • To understand how merotelic attachments impact spindle dynamics and cell division outcomes.

Main Methods:

  • Genetic induction of merotelic attachments in fission yeast.
  • Laser ablation of spindle microtubules to assess force dependence.
  • Live-cell imaging to observe kinetochore-microtubule dynamics.
  • Development and application of a mechanical force balance model.

Main Results:

  • Merotelic attachment induction led to intra-kinetochore stretching, followed by correction or disruption.
  • Microtubule forces were essential for intra-kinetochore stretching and merotelic correction.
  • Multiple merotelic chromosomes reduced spindle elongation rate, consistent with a force balance model.
  • Correction of merotelic attachments in anaphase is tension-dependent.

Conclusions:

  • Merotelic attachment correction is a tension-dependent process regulated by microtubule forces.
  • An Ase1/Prc1-dependent mechanism is required to prevent spindle collapse and ensure proper cell division.
  • Understanding merotelic attachment resolution is vital for preventing aneuploidy and associated diseases.

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