Clarifying the phenotypic spectrum associated with RAD51 partners and the proteomic interplay of RAD51 paralogs.

ABOUT THE PROJECT

Alterations in different components of the DNA repair machinery are known to be responsible for several cancer susceptibility syndromes with a high implication in breast and ovarian cancer susceptibility as well as in familial colorectal cancer. RAD51C and RAD51D paralogs were incorporated to the ovarian cancer susceptibility gene list last decade. Our group uncovered the first missense germline pathogenic variant in RAD51D that concluded to be the single most common pathogenic variant (~4%) associated with high risk for ovarian cancer in the French-Canadian population of Quebec. We described the mechanism by which the c.620C>T;p.S207L missense mutation disrupts the homologous recombination function of RAD51D and how cell lines carrying this pathogenic variant are sensitive to PARP inhibitors. Currently we focus on delineating the full phenotypic spectrum associated to germline pathogenic alterations in RAD51D and to uncover new functions of these HR-associated DNA repair genes.