Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin

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 sho...

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Detalles Bibliográficos
Autores: Sacristán, 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/369237
Acceso en línea:http://hdl.handle.net/10261/369237
https://api.elsevier.com/content/abstract/scopus_id/85194559667
Access Level:acceso abierto
Palabra clave:Centromere
Chromatin organization
Chromosomal instability
Cohesin
Condensin
Kinetochore
Mitosis
Descripción
Sumario: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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