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Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
Published on: December 5, 2017
Preparation for mitosis requires gradual CDK1 activation
Karen Akopyan1, Zhiyu Hao1, Arne Lindqvist1
1Department of Cell and Molecular Biology, Karolinska Institutet, Biomedicum A7, 171 77 Stockholm, Sweden.
Abstract:
G2 phase is considered as a time in which cells prepare for the large structural changes in the following mitosis. Starting at completion of DNA replication, CDK1 and PLK1 kinase activities gradually increase throughout G2 phase until reaching levels that initiate mitosis. Here, we use a combination of experiments and a data-driven mathematical model to study the connection between DNA replication and mitosis. We find that gradual activation of mitotic kinases ensures CDK1-dependent transcription of factors required for mitosis. In addition, we find that gradual activation of CDK1 coordinates CDK1 and PLK1 activation. Conversely, shortening G2 phase by WEE1 inhibition leads to mitotic delays, which can be partially rescued by expression of constitutively active PLK1. Our results show a function for slow mitotic kinase activation through G2 phase and suggest a mechanism for how the timing of mitotic entry is linked to preparation for mitosis.
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