Rôles des protéines de réparation des cassures double-brin dans la stabilité du génome, l'anémie de Fanconi, et le cancer


Jean-Yves Masson

Centre de recherche du CHU de Québec - Hôtel Dieu de Québec


Domaine : cancer

Porgramme Chaires de recherche

Concours 2016-2017

In most developing countries, cancer is the main cause of human death together with cardiovascular diseases. The initial event for cancer formation is mutations in the genetic material. In recent years, it has been increasing clear that mutations in DNA repair enzymes such as PALB2 and BRCA2 contribute to genome instability and cancer. Increasing DNA damage in cancerous cells through radiotherapy or chemotherapy has been useful treatments for cancer. However, these approaches have several drawbacks including secondary mutations in healthy cells. Hence, we need to design more clever, and efficient approaches to kill cancer cells in the context of personalized medicine. However, to do this, we also need to understand how DNA repair enzymes function in the cell. Thus, Dr. Masson's program is divided between basic science studies of DNA repair and studies aimed at manipulating DNA repair pathways for a therapeutic benefit.

Basic science studies in the laboratory focus mainly on the characterization of DNA resection enzymes, the DNA invasion enzymes PALB2 and BRCA2, and Fanconi anemia proteins. These enzymes are highly regulated and coordonnate a process named homologous recombination which promote DNA double-strand break repair. The first and second objectives of this proposal are to study the roles of DNA resection and DNA invasion enzymes in homologous recombination. We want to understand where and why these proteins work in a cell, how they can promote genome stability.  By knowing how these proteins renders the genome stable, we can also inhibit their function in cancer cells using new inhibitors to trigger genomic instability and cell death. Dr Masson program will also greatly improve our knowledge on rare genetic disorders (such as Fanconi Anemia) that are characterized by defective DNA damage responses.