Cohesin cleavage and Cdk inhibition trigger formation of daughter nuclei

Raquel A. Oliveira, Russell S. Hamilton, Andrea Pauli, Ilan Davis, Kim Nasmyth*

*Autor correspondente para este trabalho

Resultado de pesquisarevisão de pares

135 Citações (Scopus)

Resumo

The metaphase-anaphase transition is orchestrated through proteolysis of numerous proteins by a ubiquitin protein ligase called the anaphase-promoting complex or cyclosome (APC/C). A crucial aspect of this process is sister chromatid separation, which is thought to be mediated by separase, a thiol protease activated by the APC/C. Separase cleaves cohesin, a ring-shaped complex that entraps sister DNAs. It is a matter of debate whether cohesin-independent forces also contribute to sister chromatid cohesion. Using 4D live-cell imaging of Drosophila melanogaster syncytial embryos blocked in metaphase (via APC/C inhibition), we show that artificial cohesin cleavage is sufficient to trigger chromosome disjunction. This is nevertheless insufficient for correct chromosome segregation. Kinetochore-microtubule attachments are rapidly destabilized by the loss of tension caused by cohesin cleavage in the presence of high Cdk1 (cyclin-dependent kinase 1) activity, as occurs when the APC/C cannot destroy mitotic cyclins. Metaphase chromosomes undergo a bona fide anaphase when cohesin cleavage is combined with Cdk1 inhibition. We conclude that only two key events, opening of cohesin rings and downregulation of Cdk1, are sufficient to drive proper segregation of chromosomes in anaphase.

Idioma originalEnglish
Páginas (de-até)185-192
Número de páginas8
RevistaNature Cell Biology
Volume12
Número de emissão2
DOIs
Estado da publicaçãoPublicado - fev. 2010
Publicado externamenteSim

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