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

• Type: Article in International Scientific Journal
• Date: 2021

Authors

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

Journal

Title: Cell Reports

Vol. 37

ISSN: 2211-1247

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 22