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Phosphorylation State Defines Discrete Roles for Monopolin in Chromosome Attachment and Spindle Elongation

Authors: Choi, Sung Hugh; Péli-Gulli, Marie-Pierre; Mcleod, Iain; Sarkeshik, Ali; Yates, John R. III; Simanis, Viesturs; McCollum, Dannel;

Phosphorylation State Defines Discrete Roles for Monopolin in Chromosome Attachment and Spindle Elongation

Abstract

It is unknown how oscillations in Cdk1 activity drive the dramatic changes in chromosome and spindle dynamics that occur at the metaphase/anaphase transition.We show that the Schizosaccharomyces pombe monopolin complex has distinct functions in metaphase and anaphase that are determined by the phosphorylation state of its Mde4 subunit. When Cdk1 activity is high in metaphase, Mde4 is hyperphosphorylated on Cdk1 phosphorylation sites and localizes to kinetochores. A nonphosphorylatable mutant of Mde4 does not localize to kinetochores, appears prematurely on the metaphase spindle, and interferes with spindle dynamics and chromosome segregation, illustrating the importance of Cdk1 phosphorylation in regulating metaphase monopolin activity. When Cdk1 activity drops in anaphase, dephosphorylation of Mde4 triggers monopolin localization to the mitotic spindle, where it promotes spindle elongation and integrity, coupling the late mitotic loss of Cdk1 activity to anaphase spindle dynamics.Together, these findings illustrate how the sequential phosphorylation and dephosphorylation of monopolin helps ensure the orderly execution of discrete steps in mitosis.

Countries
Switzerland, United States
Keywords

Saccharomyces cerevisiae Proteins, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Recombinant Fusion Proteins, Cell Cycle Proteins, Saccharomyces cerevisiae, Spindle Apparatus, Microbiology, Mitotic Spindle Apparatus, Chromosomes, Molecular Genetics, Chromosome Segregation, Multiprotein Complexes, CDC2 Protein Kinase, Schizosaccharomyces, Animals, CELLBIO, Schizosaccharomyces pombe Proteins, Phosphorylation, Protein Tyrosine Phosphatases, Anaphase, Kinetochores, Metaphase, Transcription Factors

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    influence
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
18
Average
Average
Top 10%
Green
hybrid