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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
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| 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 |
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Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesinSacristán, CarlosSamejima, KumikoRuiz, Lorena AndradeDeb, MoonmoonLambers, Maaike L ABuckle, AdamBrackley, Chris ARobertson, DanielHori, TetsuyaWebb, ShaunKiewisz, RobertBepler, Tristanvan Kwawegen, EloïseRisteski, PatrikVukušić, KrunoTolić, Iva MMüller-Reichert, ThomasFukagawa, TatsuoGilbert, NickMarenduzzo, DavideEarnshaw, William CKops, Geert J P LCentromereChromatin organizationChromosomal instabilityCohesinCondensinKinetochoreMitosisCentromeres 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.The work was funded by the European Research Council (ERC-SyG 855158 [G.J.P.L.K. and I.M.T.] and ERC-CoG 648050 [D.M.]), the Netherlands Organization for Scientific Research (NWO/OCENW.KLEIN.182 [G.J.P.L.K.]), the Wellcome Trust (Principal Research Fellowship 107022 [W.C.E.]), the UK Medical Research Council (MR/J00913X/1 and MC_UU_00007/13 [N.G.]), the Deutsche Forschungsgemeinschaft (MU 1423/8-2 and MU 1423/8-3, projectno. 258577783 [T.M.-R.]), the Marie Sklodowska-Curie program (675737 [R.K. and T.M.-R.]), the Simons Foundation (SF349247 [R.K. and T.B.]), the Japan Science and Technology Agency (CREST, JPMJCR21E6 [T.F.]), and the Japan Society for the Promotion Science (JSPS) (20H05389, 21H05752, 22H00408, and 22H0469 [T.F.]). The Earnshaw lab is supported by the WCB bioinformatics core facility (core grant 203149 to the Wellcome Centre for Cell Biology).Peer reviewedCell PressEuropean CommissionNetherlands Organization for Scientific ResearchWellcome TrustMedical Research Council (UK)Japan Society for the Promotion of ScienceSimons FoundationJapan Science and Technology AgencyGerman Research FoundationKiewisz, Robert [0000-0003-2733-4978]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/369237https://api.elsevier.com/content/abstract/scopus_id/85194559667reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésCellapplication/pdfhttps://doi.org/10.1016/j.cell.2024.04.014Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3692372026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin |
| title |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin |
| spellingShingle |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin Sacristán, Carlos Centromere Chromatin organization Chromosomal instability Cohesin Condensin Kinetochore Mitosis |
| title_short |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin |
| title_full |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin |
| title_fullStr |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin |
| title_full_unstemmed |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin |
| title_sort |
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin |
| dc.creator.none.fl_str_mv |
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 |
| author |
Sacristán, Carlos |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
European Commission Netherlands Organization for Scientific Research Wellcome Trust Medical Research Council (UK) Japan Society for the Promotion of Science Simons Foundation Japan Science and Technology Agency German Research Foundation Kiewisz, Robert [0000-0003-2733-4978] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Centromere Chromatin organization Chromosomal instability Cohesin Condensin Kinetochore Mitosis |
| topic |
Centromere Chromatin organization Chromosomal instability Cohesin Condensin Kinetochore Mitosis |
| description |
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. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/369237 https://api.elsevier.com/content/abstract/scopus_id/85194559667 |
| url |
http://hdl.handle.net/10261/369237 https://api.elsevier.com/content/abstract/scopus_id/85194559667 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Cell application/pdf https://doi.org/10.1016/j.cell.2024.04.014 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.publisher.none.fl_str_mv |
Cell Press |
| publisher.none.fl_str_mv |
Cell Press |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869416812908642304 |
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15.811543 |