Grant: Operating Grant

At its core, cancer is a problem of uncontrolled cell multiplication. Because genes that promote this unregulated cell division are carried on chromosomes, losing or gaining extra copies of some chromosomes is one of the most frequent ways by which cancer cells acquire the ability to grow without restraint. Our team studies how normal cells divide up their genes (as chromosomes) during cell division in order to better understand the basic mechanisms that lead to cancer formation. To achieve this, we use yeast as a simple model organism to study the regulation of chromosomes behavior during cell multiplication. 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 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 these negative charges affect condensin functions at the molecular level. The characterization of this novel mechanism will likely provide crucial insights into the specific causes of cancer, how we can detect them better and, finally, how we can treat them more efficiently.