Spindle Assembly Checkpoint (SAC)

Definition

The spindle assembly checkpoint (SAC) is a cellular mechanism that ensures the proper segregation of chromosomes during cell division. It acts as a surveillance system that monitors the attachment of chromosomes to the mitotic spindle and blocks the progression of mitosis until all chromosomes are correctly aligned on the metaphase plate.

5 Must Know Facts For Your Next Test

1. The SAC monitors the proper attachment of kinetochores to the mitotic spindle microtubules, ensuring that each chromosome is correctly aligned on the metaphase plate.
2. The SAC is activated when even a single chromosome is not properly attached to the spindle, which triggers a signaling cascade that delays the onset of anaphase and cell division.
3. Key proteins involved in the SAC include Mad1, Mad2, Bub1, BubR1, and Mps1, which form a complex that inhibits the activity of the anaphase-promoting complex (APC/C).
4. The SAC prevents the premature separation of sister chromatids and the subsequent unequal distribution of genetic material to the daughter cells, which could lead to aneuploidy and genomic instability.
5. Disruption of the SAC can lead to chromosomal segregation errors and the development of cancer, as cancer cells often exhibit chromosomal instability.

Review Questions

• Explain the role of the spindle assembly checkpoint (SAC) in ensuring accurate chromosome segregation during cell division.
  • The spindle assembly checkpoint (SAC) is a crucial mechanism that monitors the proper attachment of chromosomes to the mitotic spindle during cell division. It ensures that each chromosome is correctly aligned on the metaphase plate before allowing the cell to proceed to anaphase and the separation of sister chromatids. The SAC acts as a surveillance system, activating a signaling cascade that delays the onset of anaphase if even a single chromosome is not properly attached to the spindle. This prevents the unequal distribution of genetic material to the daughter cells, which could lead to aneuploidy and genomic instability. By maintaining the fidelity of chromosome segregation, the SAC plays a vital role in preserving the genetic integrity of the cell.
• Describe the key proteins involved in the spindle assembly checkpoint (SAC) and their function in regulating the cell division process.
  • The spindle assembly checkpoint (SAC) involves the coordinated action of several key proteins, including Mad1, Mad2, Bub1, BubR1, and Mps1. These proteins form a complex that inhibits the activity of the anaphase-promoting complex (APC/C), which is responsible for triggering the separation of sister chromatids and the progression of mitosis. When a chromosome is not properly attached to the mitotic spindle, the SAC proteins detect this defect and activate a signaling cascade that delays the onset of anaphase. This allows the cell to correct the attachment issues before proceeding with cell division, ensuring the accurate segregation of chromosomes to the daughter cells. The proper functioning of the SAC is crucial in maintaining genomic stability and preventing the development of chromosomal abnormalities that can lead to cancer.
• Analyze the consequences of a disrupted spindle assembly checkpoint (SAC) and its potential implications for cellular health and disease development.
  • Disruption of the spindle assembly checkpoint (SAC) can have serious consequences for cellular health and lead to the development of various diseases, particularly cancer. When the SAC is compromised, the cell is unable to effectively monitor and correct errors in chromosome attachment to the mitotic spindle. This can result in the premature separation of sister chromatids and the unequal distribution of genetic material to the daughter cells, a condition known as aneuploidy. Aneuploidy is a hallmark of many cancer cells and is associated with chromosomal instability, which can further drive the accumulation of genetic mutations and the development of more aggressive cancer phenotypes. Additionally, a dysfunctional SAC can allow cells with damaged or misaligned chromosomes to progress through the cell cycle, leading to the propagation of genomic instability and the potential for the development of various cancers. Understanding the critical role of the SAC in maintaining chromosomal integrity is essential for developing targeted therapies and interventions to address the underlying causes of cancer and other genetic disorders.

Related terms

Mitosis:

The process of cell division in which a single cell divides into two or more daughter cells, each with the same genetic material.

Metaphase:

The stage of mitosis in which the chromosomes are aligned at the equatorial plate of the cell, ready for separation.

Kinetochore: A protein structure that assembles on the centromere of a chromosome and serves as the attachment point for the mitotic spindle microtubules.