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Control of Cytokinesis by the mitotic cyclin dependent kinase M-CDK1

Student thesis: Doctoral thesis

Abstract

Cytokinesis is the final regulated process in the eukaryotic mitotic cell division cycle._x000D_ Cells enter cytokinesis once that chromosome segregation is satisfactorily completed._x000D_ During cytokinesis cells physically separate, giving place to two daughter cells._x000D_ Defects in the control of cytokinesis result in aneuploidies and genomic instability. A_x000D_ key controller of cytokinesis is the mitotic Cdk1 (M-Cdk1) activity. Our project_x000D_ derives from the observed correlation between the onset of cytokinesis and the_x000D_ termination of M-Cdk1 activity. Complementary to such observation, expression of a_x000D_ hyperstable allele of the mitotic cyclin Clb2, blocks cytokinesis. Thus, the very same_x000D_ activity that pushes cells into mitosis and promotes mitotic entry and anaphase, blocks_x000D_ the occurrence of premature cytokinesis. These observations suggest that one or more_x000D_ proteins, essential to trigger cytokinesis, are inhibited by M-Cdk1 phosphorylation._x000D_ The identity of such critical M-Cdk1 substrate/s is unknown. Therefore, the goal of_x000D_ this thesis is to gain insight on how M-Cdk1 prevents premature cytokinesis during_x000D_ anaphase in the model eukaryotic organism Saccharomyces cerevisiae. The thesis_x000D_ work reveals that the Mitotic Exit Network is unexpectedly partially activated in the_x000D_ presence of prevailing high M-Cdk1 activity, and drives the release of the Cdc14_x000D_ phosphatase to the cytoplasm under such conditions.
Date of Award10 Jul 2017
Original languageUndefined/Unknown
SupervisorDavid Garcia Quintana (Director)

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