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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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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Manipulation and Analysis of Cell Cycle-Dependent Processes in Budding Yeast
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Slipping past the spindle assembly checkpoint.

Radhika Subramanian1, Tarun M Kapoor

  • 1Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.

Nature Cell Biology
|November 6, 2013
PubMed
Summary

The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation by delaying cell division. Recent studies quantitatively assess the sensitivity and robustness of this critical cell cycle control mechanism.

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Accurate genome segregation is essential for cell division.
  • The spindle assembly checkpoint (SAC) is a crucial surveillance mechanism preventing premature anaphase.
  • SAC ensures proper chromosome-spindle attachment before anaphase onset.

Purpose of the Study:

  • To quantitatively evaluate the sensitivity of the SAC.
  • To assess the robustness of the SAC response to various stimuli.
  • To provide a deeper understanding of SAC regulation during mitosis.

Main Methods:

  • Utilized quantitative assays to measure SAC signaling.
  • Employed mathematical modeling to analyze SAC dynamics.
  • Performed experiments to perturb spindle attachments and observe SAC behavior.

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Main Results:

  • Demonstrated that SAC exhibits tunable sensitivity.
  • Showcased the robustness of SAC against moderate levels of spindle misattachment.
  • Identified key factors contributing to SAC's stability and responsiveness.

Conclusions:

  • The SAC is a highly sensitive and robust signaling network.
  • Quantitative analysis provides new insights into SAC's role in maintaining genomic stability.
  • Findings contribute to understanding aneuploidy and its role in diseases like cancer.