Homologous recombination (HR) repairs DNA lesions during both mitosis and meiosis, which ultimately prevents genome instability, a hallmark of cancer and aging. Several tumor suppressor genes like BRCA1 and BRCA2 and several cancer testis antigens genes including DMC1 and MEIOB catalyze different HR steps. Understanding the molecular details of HR and its regulation holds therefore potentially large public health benefits as it can be a way to optimize cancer therapies, prevent genome instability in aged cells and fix some sterility issues. The lab expertise relies on genetics and genomics approaches to study HR during both mitosis and meiosis. The most likely project is a structure-function study of the mitotic recombinase Rad51 and its meiotic paralog Dmc1. While both are capable of catalyzing recombination, Dmc1 is more tolerant to DNA mismatches than Rad51. The goal of the project is to understand the molecular basis of this difference by mutagenizing Rad51 to find mutants allowing recombination in the presence of DNA mismatches. This will ultimately allow a better understanding of the balance between homologous and homeologous recombination, which is particularly relevant for the human genome that contains highly repeated homeologous sequences.
Les mitochondries nouvelles cibles thérapeutiques potentielles dans le cancer du pancréas -