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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.
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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
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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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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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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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Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.
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Related Experiment Video

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Manipulation and Analysis of Cell Cycle-Dependent Processes in Budding Yeast
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A RHO Small GTPase Regulator ABR Secures Mitotic Fidelity in Human Embryonic Stem Cells.

Masatoshi Ohgushi1, Maki Minaguchi2, Mototsugu Eiraku3

  • 1Human Stem Cell Technology Unit, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; Laboratory for in Vitro Histogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.

Stem Cell Reports
|June 6, 2017
PubMed
Summary

ABR protein is crucial for accurate cell division in human embryonic stem cells (hESCs). Its depletion leads to chromosome errors and aneuploidy, impacting stem cell genetic stability.

Keywords:
ABRRHO family small GTPasesaneuploidycell-cell communicationhuman embryonic stem cellsmitotic fidelity

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Area of Science:

  • Stem cell biology
  • Genetics
  • Cell biology

Background:

  • Human pluripotent stem cells (hESCs) self-renew but can acquire aneuploidy in culture.
  • This genetic instability is a barrier to clinical applications of hESCs.
  • ABR, a regulator of RHO GTPases, has known roles in hESC apoptosis.

Purpose of the Study:

  • To investigate the biological roles of ABR in human embryonic stem cells (hESCs).
  • To determine ABR's function in maintaining genetic integrity during hESC self-renewal.
  • To elucidate the mechanisms by which ABR influences mitotic fidelity.

Main Methods:

  • Studied the role of ABR in human embryonic stem cells (hESCs).
  • Investigated the impact of ABR depletion on cell division and genetic stability.
  • Analyzed centrosome dynamics, chromosome alignment, and segregation in hESCs.

Main Results:

  • ABR is essential for faithful cell division in hESCs, not directly for survival unless cell contact is lost.
  • ABR depletion disrupts centrosome dynamics.
  • Loss of ABR leads to chromosome misalignment and missegregation, increasing aneuploidy frequency.

Conclusions:

  • ABR plays a critical role in ensuring accurate mitotic processes in hESCs.
  • ABR is vital for maintaining the genetic integrity of self-renewing hESCs.
  • Understanding ABR's function provides insights into preventing aneuploidy in stem cell cultures.