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Related Concept Videos

The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

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...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

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...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

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.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

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...
Spindle Assembly02:50

Spindle Assembly

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.
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Meiosis II02:02

Meiosis II

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.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...

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Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
10:09

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Published on: September 13, 2022

Requirement for proteolysis in spindle assembly checkpoint silencing.

Roberta Visconti1, Luca Palazzo, Domenico Grieco

  • 1CEINGE Biotecnologie Avanzate, Naples, Italy.

Cell Cycle (Georgetown, Tex.)
|January 19, 2010
PubMed
Summary

Spindle assembly checkpoint (SAC) silencing requires proteolysis to resolve the Mad2-Cdc20 complex. This process involves okadaic acid-resistant phosphatases reversing key phosphorylations, ensuring accurate chromosome segregation.

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Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
09:16

Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing

Published on: October 11, 2015

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Anaphase initiation depends on the Anaphase Promoting Complex/Cyclosome (APC/C) and its coactivator Cdc20.
  • The spindle assembly checkpoint (SAC), involving proteins like Mad2 and BubR1, restrains APC/C(Cdc20) until spindle assembly to prevent chromosome segregation errors.

Purpose of the Study:

  • To investigate the mechanism of SAC silencing during mammalian cell division.
  • To elucidate how the Mad2-Cdc20 complex is resolved to allow for timely SAC inactivation and chromosome segregation.

Main Methods:

  • Analysis of Mad2-Cdc20 complex dynamics during prometaphase and metaphase in mammalian cells.
  • Investigation of the role of proteolysis in Mad2-Cdc20 complex dissociation.
  • Assessment of the effects of kinase inhibitors (CDK, Aurora) and phosphatase inhibitors (okadaic acid) on complex resolution.

Main Results:

  • The Mad2-Cdc20 complex peaks in prometaphase and its dissociation coincides with spindle assembly, requiring proteolysis.
  • Proteolysis is essential for resolving the Mad2-Cdc20 complex, not for metaphase spindle assembly.
  • Mad2-Cdc20 complex dissociation is reversed by CDK or Aurora kinase inhibition but is resistant to okadaic acid, suggesting phosphatase involvement.

Conclusions:

  • SAC silencing in mammalian cells necessitates proteolysis-dependent activation of specific phosphatases.
  • These phosphatases reverse phosphorylations that maintain the Mad2-Cdc20 complex, facilitating its disassembly.
  • This mechanism ensures accurate chromosome segregation by timely SAC inactivation.