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Updated: Nov 15, 2025
Examination of Mitotic and Meiotic Fission Yeast Nuclear Dynamics by Fluorescence Live-cell Microscopy
Published on: June 24, 2019
Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8
Haitong Hou1,2, Eftychia Kyriacou3,4, Rahul Thadani5,3
1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Haitong.hou@cuanschutz.edu.
Abstract:
Meiotic processes are potentially dangerous to genome stability and could be disastrous if activated in proliferative cells. Here we show that two key meiosis-defining proteins, the topoisomerase Spo11 (which forms double-strand breaks) and the meiotic cohesin Rec8, can dismantle centromeres. This dismantlement is normally observable only in mutant cells that lack the telomere bouquet, which provides a nuclear microdomain conducive to centromere reassembly1; however, overexpression of Spo11 or Rec8 leads to levels of centromere dismantlement that cannot be countered by the bouquet. Specific nucleosome remodelling factors mediate centromere dismantlement by Spo11 and Rec8. Ectopic expression of either protein in proliferating cells leads to the loss of mitotic kinetochores in both fission yeast and human cells. Hence, while centromeric chromatin has been characterized as extraordinarily stable, Spo11 and Rec8 challenge this stability and may jeopardize kinetochores in cancers that express meiotic proteins.
Insights
Meiosis proteins Spo11 and Rec8 dismantle centromeres, challenging genome stability. Overexpression or ectopic expression in proliferating cells can lead to kinetochore loss, with implications for cancer.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Meiosis is crucial for sexual reproduction but poses risks to genome stability.
- Centromeres are vital for chromosome segregation, and their stability is paramount.
- Meiosis-specific proteins like Spo11 and Rec8 are essential for meiotic processes.
Purpose of the Study:
- To investigate the centromere-dismantling capabilities of meiosis-defining proteins Spo11 and Rec8.
- To understand the role of the telomere bouquet in counteracting centromere dismantlement.
- To determine the consequences of ectopic expression of Spo11 and Rec8 in proliferative cells.
Main Methods:
- Utilizing fission yeast and human cell models.
- Overexpressing Spo11 and Rec8 to assess centromere stability.
- Investigating the involvement of nucleosome remodeling factors.
- Analyzing kinetochore integrity in proliferating cells.
Main Results:
- Spo11 and Rec8 were found to dismantle centromeres, a process normally suppressed by the telomere bouquet.
- Overexpression of Spo11 or Rec8 overwhelmed the bouquet's protective effect.
- Specific nucleosome remodeling factors mediate this dismantlement.
- Ectopic expression of Spo11 or Rec8 in proliferating cells resulted in loss of mitotic kinetochores.
Conclusions:
- Centromeric chromatin is not as stable as previously thought, being vulnerable to Spo11 and Rec8.
- The findings suggest a potential mechanism by which meiotic proteins could jeopardize kinetochores in cancers.
- This research highlights a critical interplay between meiotic factors and centromere integrity.
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