An anaphase surveillance mechanism prevents micronuclei formation from frequent chromosome segregation errors

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Orr, B (Autor) Outra; De Sousa, F (Autor) Outra; Gomes, AM (Autor) Outra; Afonso, O (Autor) Outra; Ferreira, LT (Autor) Outra; Figueiredo, AC (Autor) Outra; Helder Maiato (Autor) FMUP

Revista

Título: Cell Reports

Vol. 37

ISSN: 2211-1247

Editora: Elsevier

Indexação

ISI Web of Knowledge - 5 Citações

Outras Informações

ID Authenticus: P-00V-R1J

DOI: 10.1016/j.celrep.2021.109783

Abstract (EN): Micronuclei are a hallmark of cancer and several other human disorders. Recently, micronuclei were implicated in chromothripsis, a series of massive genomic rearrangements that may drive tumor evolution and progression. Here, we show that Aurora B kinase mediates a surveillance mechanism that integrates error correction during anaphase with spatial control of nuclear envelope reassembly to prevent micronuclei formation. Using high-resolution live-cell imaging of human cancer and non-cancer cells, we uncover that anaphase lagging chromosomes are more frequent than previously anticipated, yet they rarely form micronuclei. Micronuclei formation from anaphase lagging chromosomes is prevented by a midzone-based Aurora B phosphorylation gradient that stabilizes kinetochore-microtubule attachments and assists spindle forces required for anaphase error correction while delaying nuclear envelope reassembly on lagging chromosomes, independently of micro tubule density. We propose that a midzone-based Aurora B phosphorylation gradient actively monitors and corrects frequent chromosome segregation errors to prevent micronuclei formation during human cell division.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 22