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

• Autor(a) principal: Orr, B
• Data de Publicação: 2021
• Outros Autores: Sousa, F, Gomes, AM, Afonso, O, Ferreira, LT, Figueiredo, AC, Maiato, H
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/155827
• topic: Anaphase; Aurora B; Chromosome separation checkpoint; Error correction; Kinetochore; Micronuclei; Mitosis; Nuclear envelope; Phosphorylation gradient; Spindle midzone

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 microtubule 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.