ArticleThe EMBO journal2024
A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Molecular anatomy of PLK1 master docking motifs.Nature communications · 2026Article
- Sororin locks the DNA-exit gate of cohesin to preserve sister-chromatid cohesion.Nature communications · 2026Article
- Revisiting the question: When is a centromere not a kinetochore?Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025Review
- Cohesin-mediated stabilization of the CCAN complex at kinetochores in mitosis.Current biology : CB · 2025Article
- A chromatin-remodeling-independent role for ATRX in protecting centromeric cohesion.The EMBO journal · 2025Article
- Molecular mechanism of condensin I activation by KIF4A.The EMBO journal · 2025Article
- Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Vertebrate centromere architecture: from chromatin threads to functional structures.Chromosoma · 2024Review
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Authors and funding
13 authors.
Funding
Abstract
The 16-subunit Constitutive Centromere-associated Network (CCAN)-based inner kinetochore is well-known for connecting centromeric chromatin to the spindle-binding outer kinetochore. Here, we report a non-canonical role for the inner kinetochore in directly regulating sister-chromatid cohesion at centromeres. We provide biochemical, X-ray crystal structure, and intracellular ectopic localization evidence that the inner kinetochore directly binds cohesin, a ring-shaped multi-subunit complex that holds sister chromatids together from S-phase until anaphase onset. This interaction is mediated by binding of the 5-subunit CENP-OPQUR sub-complex of CCAN to the Scc1-SA2 sub-complex of cohesin. Mutation in the CENP-U subunit of the CENP-OPQUR complex that abolishes its binding to the composite interface between Scc1 and SA2 weakens centromeric cohesion, leading to premature separation of sister chromatids during delayed metaphase. We further show that CENP-U competes with the cohesin release factor Wapl for binding the interface of Scc1-SA2, and that the cohesion-protecting role for CENP-U can be bypassed by depleting Wapl. Taken together, this study reveals an inner kinetochore-bound pool of cohesin, which strengthens centromeric sister-chromatid cohesion to resist metaphase spindle pulling forces.
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