Project : Novel cytosolic nucleic acids detection routes

Genotoxic stress is a complex phenomenon engaging numerous molecular interactions and post-translational modifications, induced by genetic instability and DNA replication stress. Genotoxic stress response proteins are direct regulators of the innate immune response via (i) their ability to recognize non-canonical nucleic acid structures, including endogenous DNAs present in the cytosol, and (ii) regulation of DNA repair. There is ample evidence to suggest the existence of DNA recognition pathways distinct from the canonical cGAS-STING pathway and that operate in a tissue or cell type-dependent manner. We use a range of in vivo and in vitro techniques to identify these novel DNA recognition pathways, their interconnection with canonical pathways, and their impact on the activation of anti-tumor immune responses.