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TitleNucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity.
Journal, issue, pagesEMBO J, Vol. 44, Issue 22, Page 6556-6597, Year 2025
Publish dateOct 27, 2025
AuthorsAnjitha Gireesh / Maria Alba Abad / Ryu-Suke Nozawa / Paula Sotelo-Parrilla / Léa C Dury / Mariia Likhodeeva / Martin Wear / Christos Spanos / Cristina Cardenal Peralta / Juri Rappsilber / Karl-Peter Hopfner / Marcus D Wilson / Willem Vanderlinden / Toru Hirota / A Arockia Jeyaprakash /
PubMed AbstractThe chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B kinase) ensures accurate chromosome segregation by orchestrating sister chromatid cohesion, error correction of kinetochore- ...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.
External linksEMBO J / PubMed:41145915 / PubMed Central
MethodsEM (single particle)
Resolution2.83 - 3.8 Å
Structure data

54924

9si3

EMDB-54924, PDB-9si3:
Chromosomal Passenger Complex in complex with H3T3ph Nucleosome
Method: EM (single particle) / Resolution: 2.83 Å

54926

9si9

EMDB-54926, PDB-9si9:
Chromosomal Passenger Complex in complex with H3T3ph Nucleosome (Class0)
Method: EM (single particle) / Resolution: 2.86 Å

54938

9sj5

EMDB-54938, PDB-9sj5:
Chromosomal Passenger Complex in complex with H3T3ph Nucleosome (Class1)
Method: EM (single particle) / Resolution: 2.85 Å

55003

9slj

EMDB-55003, PDB-9slj:
Chromosomal Passenger Complex in complex with H3T3ph Nucleosome (Double Occupancy)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-55012: Chromosomal Passenger Complex in complex with H3T3ph Nucleosome (Double Occupancy map)
Method: EM (single particle) / Resolution: 3.0 Å

Source
  • homo sapiens (human)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
KeywordsCELL CYCLE / Nucleosome-binding DNA-binding Stabilising Nucleosome Acidic-patch interaction

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