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Updated: Feb 5, 2026

Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
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Nuclear envelope assembly defects link mitotic errors to chromothripsis.

Shiwei Liu1,2,3, Mijung Kwon1,2,3, Mark Mannino1,2,3

  • 1Howard Hughes Medical Institute, Chevy Chase, MD, USA.

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|September 21, 2018
PubMed
Summary
This summary is machine-generated.

Defects in nuclear envelope assembly cause micronuclei fragility, leading to DNA damage and cancer. Spindle microtubules block essential protein import into micronuclei, causing genome instability.

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Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Nuclear envelope defects are linked to human diseases.
  • Micronuclei formation can lead to chromothripsis, a major driver of cancer.
  • The cause of micronuclear envelope fragility remains unknown.

Purpose of the Study:

  • Investigate the molecular basis of micronuclear envelope fragility.
  • Identify factors contributing to DNA damage and genome instability in micronuclei.

Main Methods:

  • Studied nuclear envelope assembly in micronuclei using advanced microscopy.
  • Analyzed the import of core and non-core nuclear envelope proteins.
  • Investigated the role of spindle microtubules in nuclear envelope formation.

Main Results:

  • Micronuclei exhibit defective nuclear envelope assembly, with inefficient import of non-core proteins like nuclear pore complexes (NPCs).
  • Spindle microtubules impede NPC assembly on lagging chromosomes, causing irreversible nuclear envelope defects.
  • Separating chromosomes from the spindle corrects these defects and prevents DNA damage.

Conclusions:

  • Micronuclear envelope fragility stems from defective assembly caused by spindle microtubules blocking NPC formation.
  • Loose coordination between chromosome segregation and nuclear envelope assembly during mitotic exit contributes to genome instability.
  • Lack of precise checkpoint controls during mitotic exit may explain frequent errors and catastrophic genome rearrangements.