Project 445992

Our bodies are sophisticated structures composed of trillions of cells. To build them, a single cell (the zygote) has to undergo billions of cell divisions, each of them requiring the duplication of our genome. Each chromosome in our genome is a very long DNA molecule carrying a sequence of a four-letter code. Cells succeed in transferring the information in DNA without corrupting it by the use of multiple specialized mechanisms. Despite of these processes, mutations still end up accumulating in our body. Interestingly, a significant fraction of these mutations is acquired in our cells during the process of genome duplication. The molecular machine that copies DNA will encounter obstacles and lesions as it copies DNA, some of which can lead to changes in DNA. Hence the sites of DNA synthesis in the cell are also the points where many of the mutations originate. The purpose of this proposal is to understand how this happens. We will use sophisticated fluorescence microscopy to track relevant factors involved in this process in budding yeast. This will help us understand how mutations arise, which eventually may help to design strategies to prevent or exploit them. This work has implications for the generation, progression and control of genetic diseases, such as cancer.