Grant: Project Grant

Any mistake in the transmission of our genetic material is sufficient to generate genome instability, one of the most potent stimulator of cancer development. The overall objective of this proposal is to understand how living organisms promote effective separation of chromosomes during cell division. To achieve this objective, our team takes advantage of yeast as a simple model organism to study the regulation of chromosomes behavior during cell proliferation. This organism allows scientists to study chromosomes very efficiently because it is possible to remove genes involved in chromosome separation in yeast in ways that are not possible in other organisms. Using this approach, we have identified in our previous research key mechanisms responsible for changes in chromosome structure during cell division. The new mechanisms we identified rely on conserved enzymes that are key to normal cell division and that are also frequently misregulated in human cancers, the polo-like kinase, casein kinase and cyclin-dependent kinase. We have found that each of these players acts by adding a tag of negative charge -a simple phosphate molecule- onto an important chromosome regulator, the "condensin" factor. The next step for us is to find out how these tags of negative charge control condensin. In particular, we propose to remove the negative tags on condensin and determine how this affects the ability of cells to maintain chromosome structure and to allow effective separation of chromosomes during cell multiplication. We also want to understand how different types of tags added on condensin affect its functions at the molecular level. Ultimately, our work will have a major positive impact on human health by revealing new cellular mechanisms critical for cancer development and by identifying new genetic vulnerabilities that could be used for cancer treatment.