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 Marenduzzo; William C Earnshaw; Geert J P L Kops

doi:10.1016/j.cell.2024.04.014

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

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

11 Citaten (Scopus)

Samenvatting

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.

Originele taal-2	Engels
Pagina's (van-tot)	3006-3023.e26
Tijdschrift	Cell
Volume	187
Nummer van het tijdschrift	12
DOI's	https://doi.org/10.1016/j.cell.2024.04.014
Status	Gepubliceerd - 06 jun. 2024

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10.1016/j.cell.2024.04.014

Citeer dit

Sacristan, C., Samejima, K., Ruiz, L. A., Deb, M., Lambers, M. L. A., Buckle, A., Brackley, C. A., Robertson, D., Hori, T., Webb, S., Kiewisz, R., Bepler, T., van Kwawegen, E., Risteski, P., Vukušić, K., Tolić, I. M., Müller-Reichert, T., Fukagawa, T., Gilbert, N., ... Kops, G. J. P. L. (2024). Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin. Cell, 187(12), 3006-3023.e26. https://doi.org/10.1016/j.cell.2024.04.014

@article{82bf878030064b0782b865fbadc502dd,

title = "Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin",

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.",

keywords = "Animals, Humans, Mice, Cell Cycle Proteins/metabolism, Centromere/metabolism, Chickens, Chromosomal Proteins, Non-Histone/metabolism, Chromosome Segregation, Cohesins, Kinetochores/metabolism, Microtubules/metabolism, Mitosis, Spindle Apparatus/metabolism",

author = "Carlos Sacristan and Kumiko Samejima and Ruiz, {Lorena Andrade} and Moonmoon Deb and Lambers, {Maaike L A} and Adam Buckle and Brackley, {Chris A} and Daniel Robertson and Tetsuya Hori and Shaun Webb and Robert Kiewisz and Tristan Bepler and {van Kwawegen}, Elo{\"i}se and Patrik Risteski and Kruno Vuku{\v s}i{\'c} and Toli{\'c}, {Iva M} and Thomas M{\"u}ller-Reichert and Tatsuo Fukagawa and Nick Gilbert and Davide Marenduzzo and Earnshaw, {William C} and Kops, {Geert J P L}",

year = "2024",

month = jun,

day = "6",

doi = "10.1016/j.cell.2024.04.014",

language = "English",

volume = "187",

pages = "3006--3023.e26",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "12",

}

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 & Kops, GJPL 2024, 'Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin', Cell, vol. 187, nr. 12, blz. 3006-3023.e26. https://doi.org/10.1016/j.cell.2024.04.014

TY - JOUR

T1 - Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin

AU - Sacristan, Carlos

AU - Samejima, Kumiko

AU - Ruiz, Lorena Andrade

AU - Deb, Moonmoon

AU - Lambers, Maaike L A

AU - Buckle, Adam

AU - Brackley, Chris A

AU - Robertson, Daniel

AU - Hori, Tetsuya

AU - Webb, Shaun

AU - Kiewisz, Robert

AU - Bepler, Tristan

AU - van Kwawegen, Eloïse

AU - Risteski, Patrik

AU - Vukušić, Kruno

AU - Tolić, Iva M

AU - Müller-Reichert, Thomas

AU - Fukagawa, Tatsuo

AU - Gilbert, Nick

AU - Marenduzzo, Davide

AU - Earnshaw, William C

AU - Kops, Geert J P L

PY - 2024/6/6

Y1 - 2024/6/6

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Mice

KW - Cell Cycle Proteins/metabolism

KW - Centromere/metabolism

KW - Chickens

KW - Chromosomal Proteins, Non-Histone/metabolism

KW - Chromosome Segregation

KW - Cohesins

KW - Kinetochores/metabolism

KW - Microtubules/metabolism

KW - Mitosis

KW - Spindle Apparatus/metabolism

U2 - 10.1016/j.cell.2024.04.014

DO - 10.1016/j.cell.2024.04.014

M3 - Article

C2 - 38744280

SN - 0092-8674

VL - 187

SP - 3006-3023.e26

JO - Cell

JF - Cell

IS - 12

ER -