Roles of Transcriptional Regulators and RNA Maturation Factors in the Maintenance of Genomic Stability

点击翻译按钮获取中文摘要

We are constantly exposed to stresses that damage our genetic material and may cause mutations. Mutations lead to age-related diseases such as cancer. Fortunately, our cells are equipped with proteins that can detect damage and protect our genome from degradation. We have recently identified many novel proteins that recognize broken regions of the genome. What these proteins do to protect the genome is currently unknown. Among these factors, we found that PRP19 is particularly important for the resistance to chemotherapeutic drugs and irradiation and thus helps cells repair their DNA. To figure out how PRP19 shields our genome against mutations, we will identify the specific regions of our DNA that are protected by PRP19. We will study the characteristics of these regions and what happens to them when PRP19 is removed from cells. This will bring us an extremely precise and novel point of view on how proteins safeguard our DNA, why some places in the genome break more frequently than others and what could be done to stabilize these fragiles sites and prevent mutations. ***We will also study the roles in genome preservation of the other recently identified proteins that can interact with genome lesions to uncover novel facets of the genome protection machinery. These new proteins may one day be used as novel therapeutic targets for a variety of diseases. Finally, a major source of mutations are the clashes between gene replication which is crucial for cell renewal and gene transcription which is necessary for making proteins. We will examine the ways cells resolve the conflicts between DNA replication and transcription to understand how mutations are prevented. Our research program will thus increase our understanding of the fundamental mechanisms that allow cells to replicate their DNA and produce the proteins that are necessary for life. This information may guide us in the elaboration of novel strategies that could improve the efficiency of current anti-cancer treatments in Canada.**