ArticlePLoS genetics2020
Skp, Cullin, F-box (SCF)-Met30 and SCF-Cdc4-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A for Chromosomal Stability in Budding Yeast.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Keeping it centered: decoding the activities that regulate yeast histone H3 variant Cse4 and confine it to centromeres.Frontiers in cell and developmental biology · 2026Review
- Chromatin remodeling activity of EP400 safeguards chromosomal stability by preventing CENP-A mislocalization.Cell reports · 2025Article
- Cell cycle dependent methylation of Dam1 contributes to kinetochore integrity and faithful chromosome segregation.PLoS genetics · 2025Article
- Oncohistone H3 E97K mutation facilitates CENP-A mislocalization and chromosomal instability in budding yeast.Nucleic acids research · 2025Article
- Protein Phosphatase 1 Regulatory Subunit PNUTS Prevents CENP-A Mislocalization and Chromosomal Instability.Molecular and cellular biology · 2025Article
- The Yeast F-Box Protein Met30 Regulates Proline Utilization Independently of Transceptor Can1 Under Nutrient-Rich Conditions.Microorganisms · 2024Article
- Mck1-mediated proteolysis of CENP-A prevents mislocalization of CENP-A for chromosomal stability in Saccharomyces cerevisiae.Genetics · 2024Article
- Set2 regulates Ccp1 and Swc2 to ensure centromeric stability by retargeting CENP-A.Nucleic acids research · 2024Article
- Cadmium binding by the F-box domain induces p97-mediated SCF complex disassembly to activate stress response programs.Nature communications · 2024Article
- Interaction of histone H4 with Cse4 facilitates conformational changes in Cse4 for its sumoylation and mislocalization.Nucleic acids research · 2024Article
- Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability.Molecular biology of the cell · 2023Article
- The histone H3/H4 chaperone CHAF1B prevents the mislocalization of CENP-A for chromosomal stability.Journal of cell science · 2023Article
- Adaptation to high rates of chromosomal instability and aneuploidy through multiple pathways in budding yeast.The EMBO journal · 2023Article
- Article
- Cdc48Ufd1/Npl4 segregase removes mislocalized centromeric histone H3 variant CENP-A from non-centromeric chromatin.Nucleic acids research · 2022Article
- Cdc7-mediated phosphorylation of Cse4 regulates high-fidelity chromosome segregation in budding yeast.Molecular biology of the cell · 2021Article
- Recent insights into mechanisms preventing ectopic centromere formation.Open biology · 2021Review
- Article
- Reduce, Retain, Recycle: Mechanisms for Promoting Histone Protein Degradation versus Stability and Retention.Molecular and cellular biology · 2021Review
- Reduced gene dosage of histone H4 prevents CENP-A mislocalization and chromosomal instability in Saccharomyces cerevisiae.Genetics · 2021Article
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Restricting the localization of the histone H3 variant CENP-A (Cse4 in yeast, CID in flies) to centromeres is essential for faithful chromosome segregation. Mislocalization of CENP-A leads to chromosomal instability (CIN) in yeast, fly and human cells. Overexpression and mislocalization of CENP-A has been observed in many cancers and this correlates with increased invasiveness and poor prognosis. Yet genes that regulate CENP-A levels and localization under physiological conditions have not been defined. In this study we used a genome-wide genetic screen to identify essential genes required for Cse4 homeostasis to prevent its mislocalization for chromosomal stability. We show that two Skp, Cullin, F-box (SCF) ubiquitin ligases with the evolutionarily conserved F-box proteins Met30 and Cdc4 interact and cooperatively regulate proteolysis of endogenous Cse4 and prevent its mislocalization for faithful chromosome segregation under physiological conditions. The interaction of Met30 with Cdc4 is independent of the D domain, which is essential for their homodimerization and ubiquitination of other substrates. The requirement for both Cdc4 and Met30 for ubiquitination is specifc for Cse4; and a common substrate for Cdc4 and Met30 has not previously been described. Met30 is necessary for the interaction between Cdc4 and Cse4, and defects in this interaction lead to stabilization and mislocalization of Cse4, which in turn contributes to CIN. We provide the first direct link between Cse4 mislocalization to defects in kinetochore structure and show that SCF-mediated proteolysis of Cse4 is a major mechanism that prevents stable maintenance of Cse4 at non-centromeric regions, thus ensuring faithful chromosome segregation. In summary, we have identified essential pathways that regulate cellular levels of endogenous Cse4 and shown that proteolysis of Cse4 by SCF-Met30/Cdc4 prevents mislocalization and CIN in unperturbed cells.
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