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Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
Published on: September 20, 2019
A new view of the spindle checkpoint
1Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA. hoyt@jhu.edu
The Journal of Cell Biology
|September 6, 2001
Abstract:
Previous studies of the spindle checkpoint suggested that its ability to prevent entry into anaphase was mediated by the inhibition of the anaphase-promoting complex (APC) ubiquitin ligase by Mad2. Two new studies challenge that view by demonstrating that another checkpoint protein, BubR1, is a far more potent inhibitor of APC function.
Insights
The spindle checkpoint prevents cell division errors. New research shows BubR1, not Mad2, is the key protein inhibiting the anaphase-promoting complex (APC) to halt cell cycle progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The spindle checkpoint ensures accurate chromosome segregation during cell division.
- Previous models identified Mad2 as the primary inhibitor of the anaphase-promoting complex (APC).
Purpose of the Study:
- To re-evaluate the role of Mad2 and BubR1 in inhibiting APC function during the spindle checkpoint.
- To identify the principal APC inhibitor within the spindle checkpoint pathway.
Main Methods:
- Comparative analysis of Mad2 and BubR1 protein functions.
- In vitro assays measuring APC ubiquitin ligase activity.
- Cell-based assays assessing cell cycle progression.
Main Results:
- BubR1 demonstrates significantly higher inhibitory potency against APC compared to Mad2.
- Mad2's inhibitory effect on APC is considerably weaker than previously assumed.
- BubR1 is identified as a more critical regulator of APC activity in the spindle checkpoint.
Conclusions:
- BubR1, rather than Mad2, is the predominant inhibitor of APC in the spindle checkpoint.
- This finding necessitates a revision of the current understanding of spindle checkpoint mechanisms.
- BubR1's potent APC inhibition highlights its crucial role in preventing aneuploidy.
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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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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...
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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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