Molecular characterization of the mitotic spindle checkpoint protein Bub1

• Applicant: Dr. Christiane Klebig
• Subject Area: Cell Biology
• Term: from 2006 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 31599915

Bub1, a protein kinase acting at kinetochores, performs two crucial functions during mitosis. It is essential for the spindle checkpoint and is required for correct kinetochore-microtubule attachment. It has been shown that in Bub1 depleted cells an inactive spindle checkpoint and chromosome alignment defects lead to chromosome missegregation resulting in aneuploidy and genetic instability, a hallmark of cancer cells. Interestingly, a correlation between Bub1 mutations and carcinogenesis has already been described underlining the importance of a functioning Bub1 in normal cells. It is not yet clear how Bub1 contributes at the molecular level to its different functions and whether an impairment of the functions is strong enough to cause the development of a malignant phenotype. To elucidate these questions, I plan to establish stable cell lines depleted of the endogenous Bub1 and complemented by stably integrated Bub1 mutants into the genome. The mutants will be analyzed by cell biological techniques and live cell imaging with regard to spindle checkpoint, kinetochore-microtubule attachment, and their potential to induce cell transformation.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Patrick Meraldi