Grant: Operating Grant

Any mistake in the repair of our genetic material is sufficient to generate genome instability, one of the most potent stimulator of cancer development. The central objective of this proposal is to understand how cells promote effective repair of DNA lesions. To achieve this objective, we focus our work on a family of proteins known as the Structural Maintenance of Chromosomes (SMC) proteins. Our interest in this family of proteins comes from the fact that they are known as central gatekeepers of genome stability, and mutations affecting one of these proteins cause a cancer predisposition disease, the Nijmegen Breakage Syndrome (NBS). The main aim of our work is to uncover how two SMC complexes, the Smc5-6 and Rad50 complexes, interact with damaged DNA in vitro. Then, we aim to uncover how cells regulate the behavior of these SMC complexes when they suffer DNA damage. Ultimately, our work will have a major positive impact on human health by revealing new cellular mechanisms critical for cancer development and by identifying new targets relevant for cancer treatment.