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Updated: Jul 1, 2025
05:35
Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
Published on: March 3, 2016
15.2K
Set2 regulates Ccp1 and Swc2 to ensure centromeric stability by retargeting CENP-A
Kim Kiat Lim1, Ulysses Tsz Fung Lam1, Ying Li2,3
1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Nucleic Acids Research
|March 5, 2024
Summary
Downregulating Set2 preserves centromere localization of CENP-A (centromere protein A) by redirecting it from rDNA loci. This mechanism safeguards chromosome segregation and cell viability.
Area of Science:
- Cell Biology
- Epigenetics
- Genetics
Background:
- Accurate CENP-A (centromere protein A) localization is crucial for centromere stability and chromosome segregation.
- Mislocalized CENP-A can lead to aneuploidy and cell death due to ectopic kinetochore formation.
- The mechanisms for correcting CENP-A mislocalization are not fully understood.
Purpose of the Study:
- To investigate the role of Set2 in CENP-A localization and centromere maintenance.
- To elucidate the mechanism by which mislocalized CENP-A is retargeted to the centromere.
Main Methods:
- Utilized a temperature-sensitive mutant of Schizosaccharomyces pombe CENP-A (SpCENP-A) and Set2 downregulation.
- Analyzed SpCENP-A localization, aneuploidy, and cell viability.
- Investigated the roles of Swc2, Ccp1, and canonical CENP-A loaders (Mis16, Mis17, Mis18).
Main Results:
- Set2 downregulation preserved centromere localization of SpCENP-A and reversed aneuploidy.
- Mislocalized SpCENP-A was redirected from ribosomal DNA (rDNA) loci back to the centromere.
- Set2 downregulation increased Swc2 expression, releasing Ccp1 and facilitating SpCENP-A excavation and relocalization.
Conclusions:
- Set2 plays a critical role in preventing CENP-A mislocalization.
- A novel mechanism involving Set2, Swc2, and Ccp1 facilitates the retrieval of mislocalized CENP-A to the centromere.
- This pathway is essential for maintaining genomic stability and cell viability by ensuring proper chromosome segregation.
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