1. Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin.
- Author
-
Sacristan C, Samejima K, Ruiz LA, Deb M, Lambers MLA, Buckle A, Brackley CA, Robertson D, Hori T, Webb S, Kiewisz R, Bepler T, van Kwawegen E, Risteski P, Vukušić K, Tolić IM, Müller-Reichert T, Fukagawa T, Gilbert N, Marenduzzo D, Earnshaw WC, and Kops GJPL
- Subjects
- Animals, Humans, Mice, Cell Cycle Proteins metabolism, Chickens, Chromosomal Proteins, Non-Histone metabolism, Chromosomal Proteins, Non-Histone chemistry, Chromosome Segregation, Microtubules metabolism, Spindle Apparatus metabolism, Centromere metabolism, Cohesins, Kinetochores metabolism, Mitosis
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF