BAF restricts cGAS on nuclear DNA to prevent innate immune activation

• DOI: 10.1126/science.aaw6421
• Publication Date: 2020-08-18T00:34:13Z
• Authors: Baptiste Guey; Marilena Wischnewski; Alexiane Decout; Kristina Makasheva; Murat Kaynak; Mahmut S. Sakar; Beat Fierz; Andrea Ablasser
• Keywords: Nuclear DNA; genomic DNA

The appearance of DNA in the cytosol is perceived as a danger signal that stimulates potent immune responses through cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS). How cells regulate activity cGAS toward self-DNA and guard against potentially damaging autoinflammatory fundamental biological question. Here, we identify barrier-to-autointegration factor 1 (BAF) natural opponent on genomic self-DNA. We show BAF dynamically outcompetes for binding, hence prohibiting formation DNA-cGAS complexes are essential enzymatic activity. Upon acute loss nuclear membrane integrity, necessary to restrict exposed DNA. Our observations reveal safeguard mechanism, distinct from physical separation, by which protect themselves aberrant