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Related Experiment Videos

Correcting improper chromosome-spindle attachments during cell division.

Michael A Lampson1, Kishore Renduchitala, Alexey Khodjakov

  • 1Laboratory of Chemistry and Cell Biology, Rockefeller University, New York, NY 10021, USA.

Nature Cell Biology
|February 10, 2004
PubMed
Summary

Aurora kinases correct chromosome attachment errors during cell division by selectively shortening microtubule fibers. This ensures genome integrity by properly aligning chromosomes on the mitotic spindle.

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Microtubule depolymerization at kinetochores restricts anaphase spindle elongation.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Accurate chromosome segregation during cell division requires sister kinetochores to attach to opposite spindle poles (bi-orientation).
  • Aurora kinases are crucial for regulating chromosome-microtubule attachments and are linked to oncogenesis.
  • The precise mechanism by which active Aurora kinases correct erroneous chromosome attachments remains unclear.

Purpose of the Study:

  • To investigate how active Aurora kinase corrects improper chromosome attachments during mitosis.
  • To elucidate the role of Aurora kinase in maintaining genome integrity during cell division.

Main Methods:

  • Utilized reversible small-molecule inhibitors to control Aurora kinase activity in living vertebrate cells with temporal precision.

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  • Employed real-time high-resolution microscopy to observe chromosome and microtubule dynamics during mitosis.

    • Main Results:

    • Controlled activation of Aurora kinase during mitosis corrected chromosome attachment errors.
    • Correction occurred via selective disassembly of kinetochore-microtubule fibers, not by microtubule release from kinetochores or spindle poles.
    • Mal-oriented chromosomes moved to the spindle pole as kinetochore-microtubule fibers shortened, followed by metaphase plate alignment.

    Conclusions:

    • Demonstrated a novel mechanism for correcting chromosome attachment errors mediated by Aurora kinase.
    • Provided direct evidence for selective kinetochore-microtubule fiber disassembly as a key process for maintaining genome integrity during cell division.