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Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11.
Zadra, Ivan; Jimenez-Delgado, Senda; Anglada-Girotto, Miquel; Segura-Morales, Carolina; Compton, Zachary J; Janke, Carsten; Serrano, Luis; Ruprecht, Verena; Vernos, Isabelle.
Afiliação
  • Zadra I; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Jimenez-Delgado S; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Anglada-Girotto M; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Segura-Morales C; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Compton ZJ; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Janke C; Institut Curie, Université PSL, CNRS UMR3348, F-91401, Orsay, France.
  • Serrano L; Université Paris-Saclay, CNRS UMR3348, F-91401, Orsay, France.
  • Ruprecht V; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Vernos I; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Nat Commun ; 13(1): 7147, 2022 11 21.
Article em En | MEDLINE | ID: mdl-36414642
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).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Segregação de Cromossomos / Neoplasias Limite: Animals / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Segregação de Cromossomos / Neoplasias Limite: Animals / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2022 Tipo de documento: Article