Role of the BIM1 protein on chromosome dynamics

University Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Abstract

DESCRIPTION (provided by applicant) The overall objective of this project is to characterize the nuclear function of the eukaryotic protein EB 1 using the budding yeast Saccharomyces cerevisiae as a model system. The budding yeast EB 1 homolog was identified by its ability to bind microtubules and named BIM1. EB 1 homologs have been identified in many organisms including yeast and humans. In budding yeast, fission yeast and in mammalian cells, EB 1 proteins localize to the distal tips of microtubules. The budding yeast EB 1 protein localizes to the ends of both cytoplasmic and nuclear microtubules. In the cytoplasm, it appears to link microtubules with the cell cortex through the protein Kar9. This interaction is important to properly position the nucleus and mitotic spindle at the bud neck to ensure equal separation of genetic material to the mother and daughter cells during cell division. The nuclear functions of budding yeast EB 1 have not been well characterized. I propose that in budding yeast, EB 1 serves to link microtubules with mitotic kinetochores in a manner similar to the link made between microtubules and the cell cortex in the cytoplasm. Experiments will incorporate the techniques of real-time analysis of the dynamics of chromosomes and microtubules with the advanced genetics available through budding yeast. The human EB 1 protein associates with the adenomatous polyposis coli (APC) tumor suppressor protein and mutation of APC corresponds to an early step in the development of colon cancer. Although the yeast homolog of the APC protein has not been identified, the increased understanding of the role of EB 1 in budding yeast gained through the proposed studies can be extrapolated to the human homolog because the structure and function of EB 1 proteins among organisms is conserved.