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Related Concept Videos

Inhibition of Cdk Activity02:34

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
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Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Related Experiment Video

Updated: May 17, 2025

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
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CDC6 Inhibits CDK1 Activity in MII-Arrested Oocyte Cell-Free Extract.

Louis Dillac1,2, Klaudia Porębska3, Malgorzata Kloc4,5,6

  • 1Dynamics and Mechanics of Epithelia Group, Institute of Genetics and Development of Rennes (IGDR), National Centre for Scientific Research (CNRS), Faculty of Medicine, University of Rennes, UMR 6290, 35043 Rennes, France.

International Journal of Molecular Sciences
|May 14, 2025
PubMed
Summary

Cell division cycle 6 (CDC6) silences cyclin-dependent kinase 1 (CDK1) activity in Xenopus oocytes, regulating meiotic arrest and activation. This CDC6-CDK1 interaction ensures proper cell cycle timing during oocyte maturation and transition to interphase.

Keywords:
Xenopus laeviscalciumcell cyclecell division cycle 27 (CDC27)cell division cycle 6 (CDC6)cyclin-dependent kinase 1 (CDK1)embryohistone H1 kinasemeiotic-to-mitotic transitionmetaphase II (MII) arrestoocyteoocyte activation

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Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Cyclin-dependent kinase 1 (CDK1) activity is critical for cell cycle progression.
  • Cell division cycle 6 (CDC6) regulates CDK1 in mitotic divisions.
  • The role of CDC6 in meiotic cell cycles, specifically in Metaphase II (MII)-arrested oocytes, is unknown.

Purpose of the Study:

  • To investigate the interaction between CDC6 and CDK1 in Xenopus laevis.
  • To determine the role of CDC6 in controlling CDK1 activity during MII arrest and oocyte activation.

Main Methods:

  • Utilized Xenopus laevis cell-free extracts arrested in MII (CSF extract).
  • Employed glutathione S-transferase (GST)-CDC6 pull-down assays to assess protein association.
  • Performed histone H1 kinase assays to measure CDK1 activity.
  • Analyzed changes in CDK1 substrate phosphorylation (CDC27) and used immunodepletion techniques.

Main Results:

  • CDC6 associates with CDK1 in CSF extracts and downregulates its kinase activity, contributing to MII arrest homeostasis.
  • Exogenous GST-CDC6 accelerates the MII-to-interphase transition upon calcium activation.
  • Depletion of endogenous CDC6 slows down the MII-to-interphase transition.
  • CDC6 controls the dynamics of MII to interphase transition in a dose-dependent manner.

Conclusions:

  • CDC6 functions as a CDK1 silencer in Xenopus oocytes, both during MII arrest and oocyte activation.
  • CDC6 ensures the appropriate activity and timely inactivation of CDK1 during meiotic processes.
  • This study demonstrates CDC6's crucial role in regulating CDK1 beyond mitotic divisions, extending to meiotic arrest and transition.