Spindle assembly checkpoint (SAC)

Definition

The spindle assembly checkpoint (SAC) is a crucial regulatory mechanism during cell division that ensures proper chromosome alignment and attachment to the spindle apparatus before proceeding with mitosis. It acts as a surveillance system, preventing cells from entering anaphase until all chromosomes are correctly positioned and secured, thus maintaining genomic stability.

5 Must Know Facts For Your Next Test

1. The SAC is activated by unattached or improperly attached kinetochores, which signal that the cell should delay anaphase.
2. Key proteins involved in the SAC include Mad2, BubR1, and Bub3, which work together to inhibit the anaphase-promoting complex (APC).
3. Failure of the SAC can lead to aneuploidy, where cells have an abnormal number of chromosomes, contributing to cancer progression.
4. The SAC not only monitors chromosome attachment but also integrates signals from the microtubule dynamics during mitosis.
5. Research shows that in some cancer cells, the SAC may be compromised, allowing for unchecked progression through mitosis despite incorrect chromosome alignment.

Review Questions

• How does the spindle assembly checkpoint contribute to maintaining genomic stability during cell division?
  • The spindle assembly checkpoint (SAC) ensures that all chromosomes are properly aligned and attached to the spindle before allowing the cell to proceed to anaphase. By monitoring kinetochores and their attachment to microtubules, the SAC can delay progression if any issues are detected. This regulation prevents errors in chromosome segregation, which is vital for maintaining genomic stability and preventing conditions like aneuploidy.
• What role do key proteins like Mad2 and BubR1 play in the function of the spindle assembly checkpoint?
  • Mad2 and BubR1 are critical components of the spindle assembly checkpoint that help prevent premature entry into anaphase. When kinetochores are not properly attached to microtubules, these proteins accumulate at the unattached sites and signal to inhibit the anaphase-promoting complex (APC). This inhibition ensures that all chromosomes are correctly aligned and attached before mitotic progression occurs, highlighting their essential roles in maintaining proper cell division.
• Evaluate the implications of a malfunctioning spindle assembly checkpoint in cancer cells and its potential impact on treatment strategies.
  • A malfunctioning spindle assembly checkpoint can lead to significant problems such as aneuploidy in cancer cells, which often results from improper chromosome segregation. This aberration can contribute to tumorigenesis and promote genetic diversity among cancer cells, making them more resilient to treatments. Understanding how the SAC is compromised in these cells offers insight into potential therapeutic targets, leading to strategies aimed at restoring proper checkpoint function or exploiting this weakness in cancer therapies.

Related terms

Mitosis: A phase of the cell cycle where replicated chromosomes are separated into two new nuclei, followed by cell division.

Chromosome Alignment: The process during metaphase where chromosomes line up along the metaphase plate, ensuring accurate segregation.

Anaphase:

The stage of mitosis when sister chromatids are pulled apart to opposite poles of the cell.