Grant: Project Grant

Our cells are constantly subjected to stress that can damage their genetic material and cause mutations. Mutations can lead to the development of diseases such as cancer. To prevent the occurrence of deleterious mutations, our cells harbour signaling pathways that detect the DNA structures associated with damage and protect our genomes from degradation. Cancer cells often have defects in these protective pathways and are thus more sensitive to stress and accumulate mutations more readily than healthy cells. This is leveraged by doctors to destroy tumors through the use of chemo- and radio-therapy which cause unsustainable levels of damage to the genetic material of cancer cells. In an effort to identify novel therapeutic targets that could help in the fight against cancer, we have recently identified many new proteins that can recognize the structures found at broken regions of the genome. Amongst these factors, 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 and additional PRP19-like proteins called ubiquitin ligases allows our cells to protect their DNA. We will thus examine how PRP19 works with other proteins to remove the toxic DNA lesions that may appear when cells replicate their genetic material. This new information will improve our understanding of the complex pathways that protect our DNA and guide us in the elaboration of novel strategies that will improve the efficiency of current anti-cancer treatments.