PUBLICATION
Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11
- Authors
- Zadra, I., Jimenez-Delgado, S., Anglada-Girotto, M., Segura-Morales, C., Compton, Z.J., Janke, C., Serrano, L., Ruprecht, V., Vernos, I.
- ID
- ZDB-PUB-221123-9
- Date
- 2022
- Source
- Nature communications 13: 71477147 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Chromosome Segregation*
- Humans
- Kinetochores
- Microtubules/genetics
- Neoplasms*/genetics
- Spindle Apparatus/genetics
- Zebrafish/genetics
- PubMed
- 36414642 Full text @ Nat. Commun.
Citation
Zadra, I., Jimenez-Delgado, S., Anglada-Girotto, M., Segura-Morales, C., Compton, Z.J., Janke, C., Serrano, L., Ruprecht, V., Vernos, I. (2022) Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11. Nature communications. 13:71477147.
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).
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping