Rôles des régulateurs de l'expression et de la maturation des ARNs dans le maintien de la stabilité du génome

 

Alexandre Maréchal

Université de Sherbrooke

 

Domaine : cancer

Programme chercheurs-boursiers  - Junior 1

Concours 2017-2018

Our cells are constantly exposed to stress that can damage their genetic material and cause mutations. Such mutations can lead to the development of age-related diseases such as cancer. To prevent the occurence of deleterious mutations, our cells are equipped with signaling pathways that can detect the DNA structures associated with damage and protect our genome from degradation.

We have recently identified many novel proteins that can recognize the structures found at broken regions of the genome. For the vast majority of these proteins, their role in genome protection is currently unexplored. Amongst these factors, we found that PRP19 is particularly important for the resistance to chemotherapeutic drugs and irradiation which tells us that PRP19 helps cells repair their DNA. PRP19 works by modifying other proteins in the cell such as RPA, an essential guardian of our genome.

Our work will help us understand how the modification of RPA and other proteins by PRP19 allows the cell to protect its DNA. We will also study the roles in genome preservation of other recently identified proteins that can interact with the structures found at genome lesions in order to uncover novel therapeutic targets. Finally, a major source of mutations in our genome is the interference between gene replication which is crucial for cell renewal and gene transcription which is necessary for protein production.

We will examine the cellular machines that prevent the conflicts between DNA replication and transcription to understand how our cells prevent mutation and stifle cancer onset. This novel information will guide us in the elaboration of novel strategies that will improve the efficiency of current anti-cancer treatments.