The transmission of genetic material in each cell division requires its accurate duplication and distribution to the daughter cells. Errors in this process lead to aneuploidy, which is implicated in oncogenesis, disability and cell death. The chromosomes are segregated into two equivalent parts by a microtubule-based molecular machine, the mitotic spindle. The spindle is bipolar with each pole carrying an exact complement of chromosomes to each daughter cell. Spindle morphogenesis requires spatially controlled microtubule nucleation. The small gamma-tubulin complex is required for nucleation but is surprisingly inactive in isolated form. Our recent structural advances make a strong prediction for how the complex could be activated, which we will test by a mutational analysis. Moreover we will identify components or modifications of the complex that activate and regulate nucleation. Chromosomes attach to microtubules via kinetochores, multiprotein organelles that span from the DNA to the microtubule. This connection is carefully orchestrated and controls both the movement and organization of chromosomes to ensure proper segregation. Kinetochores perform the surprising feat of maintaining strong persistent attachments to microtubules even during the addition and removal of thousand of tubulin subunits. We will continue our reconstitution of the kinetochore from component parts to understand the molecular mechanism and regulation underlying this attachment.
The transmission of genetic material in each cell division requires its accurate duplication and distribution to the daughter cells. Errors in this process lead to aneuploidy, which is implicated in oncogenesis, disability and cell death.
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