Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin

Carlos Sacristan*, Kumiko Samejima*, Lorena Andrade Ruiz, Moonmoon Deb, Maaike L. A. Lambers, Adam Buckle, Chris A. Brackley, Daniel Robertson, Tetsuya Hori, Shaun Webb, Robert Kiewisz, Tristan Bepler, Eloïse van Kwawegen, Patrik Risteski, Kruno Vukušić, Iva M. Tolić, Thomas Müller-Reichert, Tatsuo Fukagawa, Nick Gilbert, Davide MarenduzzoWilliam C. Earnshaw, Geert J.P.L. Kops*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Centromeres are scaffolds for 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 important implications for understanding the mechanisms that guarantee faithful chromosome segregation.
Original languageEnglish
Number of pages45
JournalCell
Early online date13 May 2024
DOIs
Publication statusE-pub ahead of print - 13 May 2024

Keywords / Materials (for Non-textual outputs)

  • Mitosis
  • centromere
  • kinetochore
  • chromatin organization
  • condensin
  • cohesin
  • chromosomal instability

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