2. Academic Validation
  3. Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity

Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity

  • EMBO J. 2025 Oct 27. doi: 10.1038/s44318-025-00594-y.
Anjitha Gireesh # 1,  Maria Alba Abad # 1,  Ryu-Suke Nozawa # 2,  Paula Sotelo-Parrilla 3,  Léa C Dury 4,  Mariia Likhodeeva 3,  Martin Wear 5,  Christos Spanos 6,  Cristina Cardenal Peralta 6,  Juri Rappsilber 6 7,  Karl-Peter Hopfner 3,  Marcus D Wilson 8,  Willem Vanderlinden 4,  Toru Hirota 2,  A Arockia Jeyaprakash 9 10
Affiliations

Affiliations

  • 1 Institute of Cell Biology, University of Edinburgh, Edinburgh, UK.
  • 2 Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 3 Gene Center Munich, Ludwig-Maximilians-Universität, Munich, Germany.
  • 4 School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, UK.
  • 5 Protein Production EPPF, University of Edinburgh, Edinburgh, UK.
  • 6 Discovery Research Platform for Hidden Cell Biology, University of Edinburgh, Edinburgh, UK.
  • 7 Bioanalytics, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
  • 8 Institute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, Edinburgh, UK.
  • 9 Institute of Cell Biology, University of Edinburgh, Edinburgh, UK. jeyaprakash.arulanandam@ed.ac.uk.
  • 10 Gene Center Munich, Ludwig-Maximilians-Universität, Munich, Germany. jeyaprakash.arulanandam@ed.ac.uk.
  • # Contributed equally.
PMID: 41145915 DOI: 10.1038/s44318-025-00594-y
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.

Keywords

Centromere Integrity; Chromosomal Passenger Complex; Chromosome Segregation; Kinetochore; Mitosis.

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