Grant: Operating Grant

The goal of our work is to identify and characterize genes required for mitotic chromosome transmission in yeast and to relate our studies to human biology, and in particular to human cancer. Mutations that cause a chromosome instability (CIN) phenotype in cancer cells are now widely recognized to be a major predisposing condition in cancer initiation and/or progression. Yeast has proven to be an excellent experimental model organism for the study of cell division and the chromosome transmission cycle. We will develop yeast/human cross-species comparisons to identify and characterize molecular determinants of chromosome transmission that are highly conserved in evolution, and to determine which CIN genes are mutated in cancer cells. Using yeast genetic techniques, in particular, global synthetic lethality analysis, we will also identify genes in yeast, and the corresponding human gene counterparts, that could define potential therapeutic targets for selective killing of cancer cells relative to adjacent normal tissue. The results of our proposed research will provide a basic understanding of the mechanisms of chromosome transmission, and will therefore be directly relevant to an understanding of cancer mechanisms. The results will also be useful in identifying new drug targets that could be used to screen for new cancer therapeutics for the selective killing of cancer cells in patients.