A05 - Structural mechanisms of self-nucleic acid sensing by cGAS
cGAS detects cytosolic DNA and triggers an interferon response to battle invading pathogens and genomic stress. Cytosolic DNA can arise from pathogens, but also mitochondrial and nuclear sources. We aim at understanding how cGAS is activated by pathogenic DNA and some self-DNA, but not by intact nuclear chromosomal DNA. Using cryo-EM, we revealed how mononucleosomes inhibit cGAS by nucleosomal sequestration. We now aim at deriving how cGAS interacts with more complex chromatin substrates, agonistic self-DNA, and how it can be activated in the context of aberrant chromatin.
