At a Glance
- Combining genetics with real-time analysis of living cells by video or digital enhanced microscopy to examine the role of dynein and other microtubule motor proteins in spindle and nuclear dynamics.
- Using specific chromosomal or cytoskeletal perturbations to understand cell cycle control of late mitotic events.
Accurate chromosome segregation at each cell division is one of the most fundamental processes in a living organism. This complex process requires the coordination of cytoskeletal components such as microtubules and microtubule motor proteins that form the mitotic spindle with the replication and attachment of chromosomes to the segregation apparatus. Both the high fidelity of chromosome segregation and genome integrity are essential for normal development and cellular propagation. The ease of genetic and molecular manipulations to address the mechanism of chromosome segregation n the context of a live cell makes the budding yeast an excellent model system to address the mechanism of spindle assembly and the maintenance of genome integrity in mitosis. Our lab takes a broad approach to understanding mitosis in yeast. Recent projects in the lab have addressed the role of plus end microtubule binding proteins such as Bim1 and microtubule motor proteins on spindle integrity and the contribution of pericentric chromatin to regulating spindle length.
The site of microtubule attachment to the chromosome is the kinetochore, a complex of over 60 proteins assembled at a specific site on the chromosome, the centromere. Almost every kinetochore protein identified in yeast is conserved throughout phylogeny and the organization of the kinetochore in yeast may serve as the fundamental unit of attachment for mammalian cells. More recently we have become interested in the role of two different classes of ATP binding proteins, cohesions (Smc3, Scc1) and chromatin remodeling factors (Cac1, Hir1, Rdh54), in the structural organization of the kinetochore and how these classes of proteins contribute to the fidelity of chromosome segregation.