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Related Concept Videos

The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

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The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
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Separation of Sister Chromatids02:17

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At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
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Spindle Assembly02:50

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Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
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M-Cdk Drives Transition Into Mitosis02:15

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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.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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Attachment of Sister Chromatids02:57

Attachment of Sister Chromatids

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As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules.  Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall...
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Anaphase Promoting Complex00:50

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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Updated: Dec 25, 2025

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
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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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Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint

Ping Gui1,2, Divine M Sedzro1, Xiao Yuan1

  • 1MOE Key Laboratory of Membraneless Organelle and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.

Journal of Molecular Cell Biology
|March 29, 2020
PubMed
Summary
This summary is machine-generated.

Accurate cell division relies on Mps1 kinase localization to kinetochores, regulated by interactions with the Ndc80 complex. This study reveals how Mps1 dimerization and multisite binding control its targeting, ensuring proper spindle assembly checkpoint function.

Keywords:
Mps1 kinaseNdc80 complexkinetochoremitosisspindle assembly checkpoint

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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
  • Genetics

Background:

  • Accurate chromosome segregation during mitosis is crucial for genomic stability.
  • The spindle assembly checkpoint (SAC) prevents aneuploidy by monitoring chromosome-microtubule attachments.
  • Mps1 kinase is a key upstream regulator of SAC, requiring precise kinetochore localization.

Purpose of the Study:

  • To elucidate the molecular mechanisms governing Mps1 kinase kinetochore targeting.
  • To investigate the role of Mps1-Ndc80 complex interactions in SAC regulation.
  • To understand how Mps1 dimerization and its C-terminal region contribute to SAC function.

Main Methods:

  • Biochemical assays to identify protein-protein interactions.
  • In vitro and in vivo studies of Mps1 and Ndc80 complex binding.
  • Analysis of Mps1 kinetochore localization and SAC activity upon perturbation.

Main Results:

  • Multisite interactions between Mps1 and the Ndc80 complex dictate Mps1 kinetochore localization.
  • Direct interaction was identified between the Mps1 tetratricopeptide repeat domain and the Ndc80 complex.
  • Mps1 dimerization, mediated by its C-terminal fragment, enhances kinetochore targeting and SAC activity.

Conclusions:

  • Mps1 dimerization and its multisite interactions with the Ndc80 complex are essential for robust SAC signaling.
  • Perturbing Mps1 C-tail function compromises kinetochore targeting and leads to mitotic errors.
  • These findings provide critical insights into the regulation of Mps1 kinase activity for error-free mitosis.