ArticleThe EMBO journal2020
Auto-inhibition of Mif2/CENP-C ensures centromere-dependent kinetochore assembly in budding yeast.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Structure and function of the outer kinetochore.Nature reviews. Molecular cell biology · 2026Review
- Assembly and phosphoregulatory mechanisms of the budding yeast outer kinetochore KMN complex.The Journal of cell biology · 2026Article
- Direct observation of interdependent and hierarchical kinetochore assembly on individual centromeres.Nucleic acids research · 2025Article
- Structure of the human KMN complex and implications for regulation of its assembly.Nature structural & molecular biology · 2024Article
- Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly.Current biology : CB · 2023Article
- The Four Causes: The Functional Architecture of Centromeres and Kinetochores.Annual review of genetics · 2022Review
- Comprehensive characterization of the Hsp70 interactome reveals novel client proteins and interactions mediated by posttranslational modifications.PLoS biology · 2022Article
- Kinetochore Architecture Employs Diverse Linker Strategies Across Evolution.Frontiers in cell and developmental biology · 2022Review
- Article
- Permitted and restricted steps of human kinetochore assembly in mitotic cell extracts.Molecular biology of the cell · 2021Article
- Assembly principles and stoichiometry of a complete human kinetochore module.Science advances · 2021Article
- The Proteomic Landscape of Centromeric Chromatin Reveals an Essential Role for the Ctf19Current biology : CB · 2021Article
- Biochemical evidence for diverse strategies in the inner kinetochore.Open biology · 2020Review
- Auto-inhibition of Mif2/CENP-C ensures centromere-dependent kinetochore assembly in budding yeast.The EMBO journal · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Kinetochores are chromatin-bound multi-protein complexes that allow high-fidelity chromosome segregation during mitosis and meiosis. Kinetochore assembly is exclusively initiated at chromatin containing Cse4/CENP-A nucleosomes. The molecular mechanisms ensuring that subcomplexes assemble efficiently into kinetochores only at centromeres, but not anywhere else, are incompletely understood. Here, we combine biochemical and genetic experiments to demonstrate that auto-inhibition of the conserved kinetochore subunit Mif2/CENP-C contributes to preventing unscheduled kinetochore assembly in budding yeast cells. We show that wild-type Mif2 is attenuated in its ability to bind a key downstream component in the assembly pathway, the Mtw1 complex, and that addition of Cse4 nucleosomes overcomes this inhibition. By exchanging the N-terminus of Mif2 with its functional counterpart from Ame1/CENP-U, we have created a Mif2 mutant which bypasses the Cse4 requirement for Mtw1 binding in vitro, thereby shortcutting kinetochore assembly. Expression of this Mif2 mutant in cells leads to mis-localization of the Mtw1 complex and causes pronounced chromosome segregation defects. We propose that auto-inhibition of Mif2/CENP-C constitutes a key concept underlying the molecular logic of kinetochore assembly.
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