Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity
Year: 2025
Type: article
Abstract: The chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B kinase) ensures accurate chromosome segregation by orchestrating sister chromatid cohesion, error correction of kinetochore-microtubule attachments, and spindle assembly checkpoint signaling. Correct spatiotemporal regulation of CPC is critical for its function. Phosphorylations of histone H3 Thr3 and histone H2A Thr120 and modification-independent nucleosome interactions involving Survivin and Borealin contribute to CPC centromere enrichment. However, how various nucleosome binding elements collectively contribute to CPC centromere enrichment at the mechanistic level, and whether CPC has any non-catalytic role at centromere remain open questions. Combining the high-resolution cryo-EM structure of a CPC-bound H3Thr3ph nucleosome with atomic force microscopy and biochemical and cellular assays, we demonstrate that CPC employs multipartite interactions, which facilitate its engagement with nucleosome acidic patch and the DNA entry-exit site. Perturbing the CPC-nucleosome interaction compromises chromatin protection against MNase digestion in vitro, and centromeric chromatin stability and error-free chromosome segregation in cells. Our work suggests a non-catalytic chromatin-stabilizing role of CPC in maintaining centromeric chromatin features critical for kinetochore function.
Source: The EMBO Journal
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $7,990
Funders: Wellcome Trust, UK Research and Innovation, Deutsche Forschungsgemeinschaft, Ministry of Education, Culture, Sports, Science and Technology, Darwin Trust of Edinburgh, Medical Research Council, Japan Society for the Promotion of Science, Core Research for Evolutional Science and Technology, HORIZON EUROPE European Research Council
Awards: G2304487391, G2581826908, G2954200057, Structural Basis for Centromere-Mediated Control of Error-free Chromosome Segregation, The Hidden Cell Discovery Research Platform, G4344158504, G4402981859, G4644850888, G4861126846, Molecular Mechanisms of Centromere Inheritance and Kinetochore Function, G5612862928, Mechanistic understanding of the reading and writing of DNA methylation, Crypto-Division: Discovering non-canonical mechanisms of genome transmission in the human fungal pathogen Cryptococcus neoformans, G6122521683, G6291076541, G6415687992, G7186665181, G7535452472, G764059879, Plastic regulation of chromosome dynamics in cancer, Core Funding for the Wellcome Trust Centre for Cell Biology, Mechanistic Basis for CENP-32 Mediated Regulation of Cell Division
OpenAlex ID: W4415648737