? Chromosome segregation must be a tightly regulated event to ensure that genetic information is not lost or duplicated. If separation of chromosomes begins before proper attachment of kinetochores to microtubules, missegregation events can occur, leading to aneuploidy. To prevent these dire consequences, the cell activates the spindle checkpoint in the absence of proper kinetochore-microtubule attachment to halt chromosome segregation until errors are repaired. Budding yeast will be used as a model organism to study two aspects of cell division. First, proteins needed for attachment of kinetochores to microtubules and for movement of chromosomes along microtubules will be identified. Second, the proteins at the kinetochore involved in triggering the spindle checkpoint to halt cell division will be determined. Different biochemical purification techniques will be used to isolate and analyze proteins present at the kinetochore for their role in microtubule-kinetochore attachment, chromosome movement, and checkpoint activation. A characterization of the proteins involved in chromosome segregation and checkpoint activation could lead to a greater understanding of how human diseases, such as cancer, can be prevented. ? ?
