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

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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.