New publication by the Hopfner lab on how nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity
Gireesh A, Abad MA, Nozawa RS, Sotelo-Parrilla P, Dury LC, Likhodeeva M, Wear M, Spanos C, Peralta CC, Rappsilber J, Hopfner KP, Wilson MD, Vanderlinden W, Hirota T, Jeyaprakash AA (2025) Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity. EMBO J, 44(22):6556-6597 Link
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.
Read the full paper here: https://www.embopress.org/doi/full/10.1038/s44318-025-00594-y
