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: Cell Nucleus; 0301 basic medicine; 2. Zero hunger; 0303 health sciences; Nuclear Envelope; DNA; Nucleotidyltransferases; Immunity, Innate; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; Gene Knockdown Techniques; Humans; HeLa Cells

A loose BAF puts its foot on the cGAS

A signaling pathway in vertebrates called cGAS-STING detects the presence of intracellular DNA as a surrogate for both cellular damage and viral infection. At the same time, sensing of self-DNA must be suppressed to prevent the development of autoimmune responses. Guey et al. identify barrier-to-autointegration factor 1 (BAF) as a protein that intrinsically competes with the cGAS component of this pathway for binding to genomic self-DNA. When there is a breakdown in nuclear compartmentalization, cytosolic cGAS enzymatic activity is prevented because of BAF. This work suggests that the regulation of DNA detection by the innate immune system relies on more complex mechanisms than simple physical separation alone.

Science , this issue p. 823