Utilizing yeast and mammalian approaches to identify chromosome instabilities underlying colorectal cancer in humans

The molecular mechanisms that ensure proper chromosome segregation during the division of cells are of fundamental importance to maintaining the integrity of the genome (genomic stability). In humans, genomic instabilities arising from chromosome instabilities (CIN) or missegregation are known to be implicated in the development of certain types of cancer. Mutations in genes that cause genomic instability are now recognized as being important predisposing conditions that contribute to the initiation and progression of cancer. Using budding yeast as a model, Kirk McManus hopes to identify both the non-essential and essential genes of yeast regulating CIN for comparison with mammalian cells to determine any cross-species candidate genes that contribute to genome instability. A better understanding of the genetic basis of CIN in model organisms will provide candidate genes for those CIN genes mutated in cancer. The results of this research will be directly relevant to an understanding of cancer mechanisms, and may be useful in developing strategies for cancer therapy and for sub-classification of tumors based on their CIN mutational spectrum.