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Updated: Nov 20, 2025
06:39
Live Cell Imaging of Chromosome Segregation During Mitosis
Published on: March 14, 2018
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Prolonged mitosis causes separase deregulation and chromosome nondisjunction.
Norihisa Shindo1, Makoto Otsuki1, Kazuhiko S K Uchida1
1Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Ariake 3-8-31 Koto-ku, 135-8550 Tokyo, Japan.
Cell Reports
|January 20, 2021
Summary
Delayed metaphase progression in cancer cells causes premature separase activation, leading to chromosomal bridges. Swift mitotic transitions are crucial for accurate chromosome segregation.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Biology
Background:
- Separase protease activity is essential for cleaving cohesin and enabling sister chromatid separation during mitosis.
- Separase is typically suppressed during metaphase and abruptly activated before anaphase onset, but the significance of this timing is not fully understood.
Purpose of the Study:
- To investigate the impact of prolonged metaphase on separase activation and chromosome segregation fidelity.
- To explore the role of mitotic timing in cancer cell chromosomal instability.
Main Methods:
- Utilized a separase activity probe to monitor enzyme activation.
- Experimentally extended and shortened metaphase durations in cancer cell lines and chromosomally stable diploid cells.
- Assessed anaphase bridge formation as an indicator of segregation errors.
Main Results:
- Separase was found to activate precociously during prolonged metaphase in various cancer cell lines.
- Artificial extension of metaphase in diploid cells induced premature separase activation and subsequent anaphase bridges due to incomplete cohesin removal.
- Shortening prolonged metaphase restored normal separase activation and reduced anaphase bridge formation.
Conclusions:
- Retarded metaphase progression disrupts the normal separase activation profile, impairing its enzymatic function.
- This dysregulation offers a novel explanation for chromosomal instability observed in cancers.
- Rapid mitotic progression is vital for ensuring accurate chromosome segregation and preventing genomic instability.
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