Mécanismes et régulation de la stabilité des chromosomes

 

Damien D'Amours

Institut de recherche en immunologie et cancérologie

 

Domaine : cancer

Programme chercheurs-boursiers - Senior

Concours 2015-2016

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. 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, the Stability and Maintenance of Chromosome (SMC) family of proteins. We have found that each of these players acts by binding to chromosomal DNA and using cellular energy to modify the structure of DNA. The next step for us is to find out how SMC proteins convert the chemical energy stored in ATP into a mechanical force that promotes normal DNA structure.

In particular, we propose to reduce the ability of SMC proteins to use ATP through specific mutations 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 find novel small molecules that modulate the activity of SMC proteins in cells as a means to treat cancers. Our project will likely provide crucial insights into the specific causes of cancer and how we can treat them more efficiently.