Zadra, Ivan, 1991-Jiménez-Delgado, SendaAnglada-Girotto, MiquelSegura-Morales, CarolinaCompton, Zachary J.Janke, CarstenSerrano Pubull, Luis, 1982-Ruprecht, VerenaVernos, Isabelle, 1959-2023-01-242023-01-242022Zadra 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-y2041-1723http://hdl.handle.net/10230/55412Regulation 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).application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-022-34909-yChromosome segregationMitotic spindleinfo:eu-repo/semantics/openAccess