Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin

C Sacristan and K Samejima and LA Ruiz and M Deb and MLA Lambers and A Buckle and CA Brackley and D Robertson and T Hori and S Webb and R Kiewisz and T Bepler and E van Kwawegen and P Risteski and K Vukusic and IM Tolic and T Müller-Reichert and T Fukagawa and N Gilbert and D Marenduzzo and WC Earnshaw and GJPL Kops, CELL, 187 (2024).

DOI: 10.1016/j.cell.2024.04.014

Centromeres are scaffolds for the assembly of kinetochores that ensure chromosome segregation during cell division. How vertebrate centromeres obtain a three-dimensional structure to accomplish their primary function is unclear. Using super -resolution imaging, capture -C, and polymer modeling, we show that vertebrate centromeres are partitioned by condensins into two subdomains during mitosis. The bipartite structure is found in human, mouse, and chicken cells and is therefore a fundamental feature of vertebrate centromeres. Super -resolution imaging and electron tomography reveal that bipartite centromeres assemble bipartite kinetochores, with each subdomain binding a distinct microtubule bundle. Cohesin links the centromere subdomains, limiting their separation in response to spindle forces and avoiding merotelic kinetochore-spindle attachments. Lagging chromosomes during cancer cell divisions frequently have merotelic attachments in which the centromere subdomains are separated and bioriented. Our work reveals a fundamental aspect of vertebrate centromere biology with implications for understanding the mechanisms that guarantee faithful chromosome segregation.

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