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

Ivan Zadra, Senda Jimenez-Delgado, Miquel Anglada-Girotto, Carolina Segura-Morales, Zachary J. Compton, Carsten Janke, Luis Serrano, Verena Ruprecht and Isabelle Vernos ()
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Ivan Zadra: The Barcelona Institute of Science and Technology
Senda Jimenez-Delgado: The Barcelona Institute of Science and Technology
Miquel Anglada-Girotto: The Barcelona Institute of Science and Technology
Carolina Segura-Morales: The Barcelona Institute of Science and Technology
Zachary J. Compton: The Barcelona Institute of Science and Technology
Carsten Janke: Université PSL, CNRS UMR3348
Luis Serrano: The Barcelona Institute of Science and Technology
Verena Ruprecht: The Barcelona Institute of Science and Technology
Isabelle Vernos: The Barcelona Institute of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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).

Date: 2022
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DOI: 10.1038/s41467-022-34909-y

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