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Coordination of chromatid separation and spindle elongation by antagonistic activities of mitotic and S-phase CDKs.

Liang F, Richmond D, Wang Y - PLoS Genet. (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA.

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.

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The working model for the timing control of spindle elongation by the balance of mitotic versus S-phase CDKs.
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pgen-1003319-g007: The working model for the timing control of spindle elongation by the balance of mitotic versus S-phase CDKs.

Mentions: The key to a successful cell division is the coordination of various cell cycle events. For efficient chromosome segregation, spindle elongation should follow the dissolution of sister-chromatid cohesion in an orderly fashion. The molecular mechanism that ensures this sequential order remains unclear. The absence of premature spindle elongation in cells lacking cohesion indicates a cohesion-independent mechanism that controls the timing of spindle elongation. Here we show that S-phase CDK negatively regulates spindle elongation, while mitotic CDK actives the FEAR pathway to trigger Cdc14 release, which reverses S-phase CDK-dependent protein phosphorylation and simulates spindle elongation. Therefore, the balance of mitotic vs. S-phase CDK activity is critical for the timing control of spindle elongation. We also show that S-phase CDK prevents spindle elongation in part by phosphorylating a SPB component Spc110, while dephosphorylation of Spc110 by Cdc14 likely facilitates the localization of Stu2, a plus-end tracking protein, to spindle microtubules, which may directly promotes spindle elongation by enhance microtubule polymerization [37]. Furthermore, hyperactive mitotic CDK in pds1Δ cells, where the synchrony of chromosome segregation is compromised, leads to uncoupled sister-chromatid separation and spindle elongation, resulting in chromosome mis-segregation and cell death. A model illustrating and integrating this cell cycle regulatory network is shown in Figure 7.


Coordination of chromatid separation and spindle elongation by antagonistic activities of mitotic and S-phase CDKs.

Liang F, Richmond D, Wang Y - PLoS Genet. (2013)

The working model for the timing control of spindle elongation by the balance of mitotic versus S-phase CDKs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3584997&req=5

pgen-1003319-g007: The working model for the timing control of spindle elongation by the balance of mitotic versus S-phase CDKs.
Mentions: The key to a successful cell division is the coordination of various cell cycle events. For efficient chromosome segregation, spindle elongation should follow the dissolution of sister-chromatid cohesion in an orderly fashion. The molecular mechanism that ensures this sequential order remains unclear. The absence of premature spindle elongation in cells lacking cohesion indicates a cohesion-independent mechanism that controls the timing of spindle elongation. Here we show that S-phase CDK negatively regulates spindle elongation, while mitotic CDK actives the FEAR pathway to trigger Cdc14 release, which reverses S-phase CDK-dependent protein phosphorylation and simulates spindle elongation. Therefore, the balance of mitotic vs. S-phase CDK activity is critical for the timing control of spindle elongation. We also show that S-phase CDK prevents spindle elongation in part by phosphorylating a SPB component Spc110, while dephosphorylation of Spc110 by Cdc14 likely facilitates the localization of Stu2, a plus-end tracking protein, to spindle microtubules, which may directly promotes spindle elongation by enhance microtubule polymerization [37]. Furthermore, hyperactive mitotic CDK in pds1Δ cells, where the synchrony of chromosome segregation is compromised, leads to uncoupled sister-chromatid separation and spindle elongation, resulting in chromosome mis-segregation and cell death. A model illustrating and integrating this cell cycle regulatory network is shown in Figure 7.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA.

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.

Show MeSH
Related in: MedlinePlus