Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31424385.
- Also identified by DOI 10.7554/eLife.47646 and PMC identifier 6706241.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
According to the prevailing 'clock' model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient - the 'ruler' model. Here we found that Cdk1 remains active during anaphase due to ongoing APC/C<sup>Cdc20</sup>- and APC/C<sup>Cdh1</sup>-mediated degradation of B-type Cyclins in <i>Drosophila</i> and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular 'rulers' and 'clocks' licenses mitotic exit only after proper chromosome separation.
Medical subject headings
- Anaphase
- Aurora Kinase B
- CDC2 Protein Kinase
- Cyclin B1
- Drosophila Proteins