Abstract
Because cohesion prevents sister-chromatid separation and spindle elongation, cohesion dissolution may trigger these two events simultaneously. However, the relatively normal spindle elongation kinetics in yeast cohesin mutants indicates an additional mechanism for the temporal control of spindle elongation. Here we show evidence indicating that S-phase CDK (cyclin dependent kinase) negatively regulates spindle elongation. In contrast, mitotic CDK promotes spindle elongation by activating Cdc14 phosphatase, which reverses the protein phosphorylation imposed by S-phase CDK. Our data suggest that S-phase CDK negatively regulates spindle elongation partly through its phosphorylation of a spindle pole body (SPB) protein Spc110. We also show that hyperactive S-phase CDK compromises the microtubule localization of Stu2, a processive microtubule polymerase essential for spindle elongation. Strikingly, we found that hyperactive mitotic CDK induces uncoupled spindle elongation and sister-chromatid separation in securin mutants (pds1Δ), and we speculate that asynchronous chromosome segregation in pds1Δ cells contributes to this phenotype. Therefore, the tight temporal control of spindle elongation and cohesin cleavage assure orchestrated chromosome separation and spindle elongation.
Highlights
In eukaryotic cells, spindle elongation and sister-chromatid separation are two critical mitotic events, and the coordination of these two events is essential for the fidelity of chromosome segregation
The presence of securin Pds1 prevents the cleavage of cohesin, a protein complex that holds sister chromatids together, but the degradation of Pds1 leads to robust cohesion dissolution, resulting in synchronous separation of all chromosomes
Cyclin-dependent kinases (CDKs) play a key role in the cell cycle, and it is well established that S-phase CDK promotes DNA synthesis
Summary
Spindle elongation and sister-chromatid separation are two critical mitotic events, and the coordination of these two events is essential for the fidelity of chromosome segregation. The cleavage of sister chromatid cohesion allows the sister chromatids to move toward the respective spindle pole, the spindle elongates further to pull sister chromatids into two daughter cells [1]. Because sisterchromatid cohesion prevents sister chromatid separation and spindle elongation, these two events could be coupled by the cleavage of cohesin. Cohesin cleavage is prohibited by the presence of securin (Pds1), which binds to and inhibits separase (Esp1) that cleaves cohesin Scc1/Mcd1 [2,3]. The degradation of Pds before anaphase entry alleviates the inhibition of Esp, resulting in the robust cohesin cleavage and simultaneous sister-chromatid separation [2,4,5]. Yeast cells lacking either Pds or cohesin do not show premature spindle elongation, indicating that a cohesion-independent mechanism controls the timing of spindle elongation [6]
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