35.11: The Spindle Assembly Checkpoint
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.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the segregation of chromosomes regardless of the completion of all the prerequisite steps. Consequently, the daughter cells formed may receive fewer or greater than the normal number of chromosomes. This condition with an abnormal chromosome number in a cell is called aneuploidy, which can lead to many developmental defects.
The spindle assembly checkpoint is activated by the presence of unattached or improperly attached kinetochores. Two models explain the release of the checkpoint mechanism — the attachment model and the tension model. The attachment model emphasizes that the saturation or full occupation of the kinetochores by kinetochore-microtubules causes the checkpoint mechanism to switch off. Alternatively, the tension model states that the tension generated from the attachment of the correct spindle-microtubule to the kinetochore is responsible for switching off the checkpoint mechanism. However, studies suggest that the attachment and tension mechanisms are both required to ensure the fidelity of spindle assembly checkpoint surveillance.
