Grant: Project Grant

Checkpoints in the cell exist to ensure that cellular processes are accurately accomplished. These mechanisms tend to be essential and when compromised can result in severe consequences for the cell as well as entire organisms. As an example, checkpoints have evolved to verify whether DNA and chromosomes are not damaged and are correctly and proportionally divided before they are transmitted to future offpring. Thus, the role of a checkpoint is to slow down the cell growth machinery to allow extra time for repair of the molecular errors involved. This is essential to maintain the integrity of the genome and the health of cells and organisms. Defects in these processes can result in cancer and in several inherited diseases such as Down Syndrome. Loss of chromosome segregation fidelity is alsothe leading cause of infertility and miscarriages. Therefore, understanding the molecular mechanisms of checkpoints will lead to better diagnostic, classification and therapeutic intervention opportunities for many of the associated pathologies. The project proposed here will explore the function of one particular checkpoint, the so-called Spindle Assembly Checkpoint, which ensures the accurate segregation of chromosomes when a single cell divides into two daughter cells. In particular the project will detail molecular mechanisms through which a key player in this process regulates turning on and turning off the Spindle Assembly Checkpoint.