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Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
07:14

Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations

Published on: September 20, 2019

Survivin is required for a sustained spindle checkpoint arrest in response to lack of tension

Susanne M A Lens1, Rob M F Wolthuis, Rob Klompmaker

  • 1Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

The EMBO Journal
|June 14, 2003
PubMed

Insights

Survivin is essential for proper chromosome alignment and cell division in humans. Lacking survivin prevents key proteins from attaching to chromosomes, leading to errors in cell division and polyploidy.

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Survivin is implicated in mitosis, but its precise function in human cell division is unclear.
  • Understanding survivin's role is crucial for comprehending cell cycle regulation and potential therapeutic targets.

Purpose of the Study:

  • To elucidate the specific role of survivin in mammalian cell division.
  • To investigate the impact of survivin depletion on chromosome alignment, spindle assembly checkpoint (SAC) function, and ploidy.

Main Methods:

  • Depletion of survivin in mammalian cells using genetic techniques.
  • Analysis of chromosome alignment, kinetochore protein recruitment (Aurora B, BubR1, Mad2), and cell ploidy.
  • Assessment of SAC activation and response to tension-dependent and microtubule-depolymerizing drugs.

Main Results:

  • Survivin-depleted cells exhibit failed chromosome alignment and abnormal polyploidy.
  • BubR1 and Mad2 are prematurely released from kinetochores, indicating impaired SAC function.
  • Cells lacking survivin respond to spindle disruption but not to tension-preventing drugs, highlighting a specific defect in tension sensing.

Conclusions:

  • Survivin is critical for stable kinetochore-microtubule attachments and tension generation.
  • It plays a vital role in sustained SAC signaling in response to lack of tension, ensuring accurate chromosome segregation.
  • Survivin is indispensable for maintaining genomic stability during human cell division.

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