Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11

Zadra, Ivan, 1991-; Jiménez-Delgado, Senda; Anglada-Girotto, Miquel; Segura-Morales, Carolina; Compton, Zachary J.; Janke, Carsten; Serrano Pubull, Luis, 1982-; Ruprecht, Verena; Vernos, Isabelle, 1959-

Inici
→
Recerca: articles, congressos, llibres
→
Center for Genomic Regulation (CRG)
→
Articles (Center for Genomic Regulation (CRG))
→
Visualitza element

dc.contributor.author	Zadra, Ivan, 1991-
dc.contributor.author	Jiménez-Delgado, Senda
dc.contributor.author	Anglada-Girotto, Miquel
dc.contributor.author	Segura-Morales, Carolina
dc.contributor.author	Compton, Zachary J.
dc.contributor.author	Janke, Carsten
dc.contributor.author	Serrano Pubull, Luis, 1982-
dc.contributor.author	Ruprecht, Verena
dc.contributor.author	Vernos, Isabelle, 1959-
dc.date.accessioned	2023-01-24T07:19:48Z
dc.date.available	2023-01-24T07:19:48Z
dc.date.issued	2022
dc.identifier.citation	Zadra I, Jimenez-Delgado S, Anglada-Girotto M, Segura-Morales C, Compton ZJ, Janke C, Serrano L, Ruprecht V, Vernos I. Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11. Nat Commun. 2022 Nov 21;13(1):7147. DOI: 10.1038/s41467-022-34909-y
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10230/55412
dc.description.abstract	Regulation of microtubule (MT) dynamics is key for mitotic spindle assembly and faithful chromosome segregation. Here we show that polyglutamylation, a still understudied post-translational modification of spindle MTs, is essential to define their dynamics within the range required for error-free chromosome segregation. We identify TTLL11 as an enzyme driving MT polyglutamylation in mitosis and show that reducing TTLL11 levels in human cells or zebrafish embryos compromises chromosome segregation fidelity and impairs early embryonic development. Our data reveal a mechanism to ensure genome stability in normal cells that is compromised in cancer cells that systematically downregulate TTLL11. Our data suggest a direct link between MT dynamics regulation, MT polyglutamylation and two salient features of tumour cells, aneuploidy and chromosome instability (CIN).
dc.description.sponsorship	The work was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 675737 to I.V., I.Z., and C.J.; the grants from the Spanish Ministry of Economy (MINECO) I + D grant BFU2012-37163 and BFU2015-68726-P to I.V.; C.J. was supported by the French National Research Agency (ANR) award ANR-17-CE13-0021 and Fondation pour la Recherche Medicale (FRM) grant DEQ20170336756. V.R. was supported by the Spanish Ministry of Economy (MINECO) I + D grant PID2020-117011GB-I00. We thank all the members of the Vernos group and the DiviDE ITN for the discussions and the CRG microscopy facility for technical support. We acknowledge the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa” as well as support of the CERCA Programme/Generalitat de Catalunya. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript are in part based upon data obtained from the GTEx Portal on 05/03/2021. The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.
dc.format.mimetype	application/pdf
dc.language.iso	eng
dc.publisher	Nature Research
dc.relation.ispartof	Nat Commun. 2022 Nov 21;13(1):7147
dc.rights	© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.title	Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	http://dx.doi.org/10.1038/s41467-022-34909-y
dc.subject.keyword	Chromosome segregation
dc.subject.keyword	Mitotic spindle
dc.relation.projectID	info:eu-repo/grantAgreement/EC/H2020/675737
dc.relation.projectID	info:eu-repo/grantAgreement/ES/3PN/BFU2012-37163
dc.relation.projectID	info:eu-repo/grantAgreement/ES/1PE/BFU2015-68726-P
dc.relation.projectID	info:eu-repo/grantAgreement/ES/2PE/PID2020-117011GB-I00
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.type.version	info:eu-repo/semantics/publishedVersion