Details

Autor(en) / Beteiligte

• Orr, Bernardo
• De Sousa, Filipe
• Gomes, Ana Margarida
• Afonso, Olga
• Ferreira, Luísa T.
• Figueiredo, Ana C.
• Maiato, Helder

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2021-11, Vol.37 (6), p.109783-109783, Article 109783

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Anaphase lagging chromosomes are frequent but rarely form micronuclei•A midzone Aurora B activity gradient prevents micronuclei from segregation errors•Midzone Aurora B assists spindle forces at the kinetochores to correct errors•Aurora B spatially regulates nuclear envelope reformation on lagging chromosomes Orr et al. show that a spindle midzone-based Aurora B phosphorylation gradient mediates a surveillance mechanism that prevents micronuclei formation from frequent chromosome segregation errors by integrating error correction during anaphase with spatial control of nuclear envelope reassembly on lagging chromosomes in human cells.