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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...
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.
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 microtubule array...
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...
The Mitotic Spindle02:27

The Mitotic Spindle

The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...
The Mitotic Spindle02:27

The Mitotic Spindle

The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...

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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

Deficient spindle assembly checkpoint in multiple myeloma.

Elena Díaz-Rodríguez1, Stela Álvarez-Fernández, Xi Chen

  • 1Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Salamanca, Spain. ediaz@usal.es

Plos One
|December 2, 2011
PubMed
Summary

Multiple myeloma (MM) plasma cells show altered spindle assembly checkpoint (SAC) components and function. Restoring SAC protein levels improved chromosome segregation, suggesting SAC as a potential therapeutic target for MM.

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Area of Science:

  • Hematology
  • Cell Biology
  • Cancer Research

Background:

  • Multiple myeloma (MM) is a plasma cell malignancy characterized by significant cytogenetic abnormalities.
  • A hallmark of MM is aneuploidy, often linked to spindle assembly checkpoint (SAC) dysfunction.
  • Understanding SAC alterations is crucial for identifying novel MM therapeutic strategies.

Purpose of the Study:

  • To investigate the functionality of the spindle assembly checkpoint (SAC) in multiple myeloma (MM) cells.
  • To identify alterations in SAC components and their impact on chromosomal stability in MM.
  • To evaluate the potential of targeting the SAC pathway for MM treatment.

Main Methods:

  • Analysis of SAC component RNA and protein levels in MM cell lines.
  • Assessment of chromosome segregation following manipulation of SAC protein content.
  • Functional testing of SAC by exposing cells to microtubule-disrupting agents.

Main Results:

  • While RNA levels of most SAC components were conserved, several key proteins (e.g., MAD2, CDC20) showed reduced protein content in MM cell lines.
  • Restoring protein levels of SAC components improved chromosome segregation accuracy without significantly impacting cell growth.
  • A majority of MM cell lines exhibited functional defects in the SAC when challenged with microtubule-disrupting agents.

Conclusions:

  • Alterations in both the expression and function of SAC components are prevalent in multiple myeloma.
  • The identified SAC defects contribute to chromosomal instability in MM.
  • The spindle assembly checkpoint represents a promising therapeutic target for multiple myeloma treatment.