Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin

Sacristan, Carlos; Samejima, Kumiko; Ruiz, Lorena Andrade; Deb, Moonmoon; Lambers, Maaike L.A.; Buckle, Adam; Brackley, Chris A.; Robertson, Daniel; Hori, Tetsuya; Webb, Shaun; Kiewisz, Robert; Bepler, Tristan; van Kwawegen, Eloïse; Risteski, Patrik; Vukušić, Kruno; Tolić, Iva M.; Müller-Reichert, Thomas; Fukagawa, Tatsuo; Gilbert, Nick; Marenduzzo, Davide; Earnshaw, William C.; Kops, Geert J.P.L. (2024) Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin. Cell . ISSN 0092-8674

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	mitosis; centromere; kinetochore; chromatin organization; condensin; cohesin; chromosomal instability
Subjects:	NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Biology
Depositing User:	Ivan Markotić
Date Deposited:	29 May 2024 06:48
URI:	http://fulir.irb.hr/id/eprint/8874
DOI:	10.1016/j.cell.2024.04.014

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