PIF2024 - DNA damage tolerance mechanisms and links to nuclear proteostasis networks in the maintenance of cellular homeostasis (PID2023-148435NB-I00)

The general goal of this proposal is to contribute to the knowledge of the mechanisms involved in preventing genomic instability, a hallmark of cancer and other diseases as well as a feature of premature aging, developmental abnormalities and neurological disorders. A major cause of genome instability is the presence of unrepaired DNA damage, and the project will mainly address the study of how DNA damage tolerance pathways help maintain genome integrity in proliferating cells. Moreover, we will investigate how these mechanisms interact with proteostasis networks in the maintenance of cellular homeostasis. The methodology will combine in vivo and in vitro studies and will include molecular biology, genetics, cell biology and biochemistry techniques. Since the processes to be studied are evolutionary conserved, the genetically tractable yeast Saccharomyces cerevisiae will be used as a working eukaryotic model. S. cerevisiae is indeed a powerful tool for in-depth study of fundamental biological problems and has been very useful in establishing the molecular basis of different pathologies.