Figure 3.

The mechanism of cGAS inactivation in the nucleus. (A) In nucleosome independent way, the N-terminal chromatin sensing region of cGAS or S305 is hyperphosphorylated by mitotic kinase. What’s more, the competitive binding of BAF or cia-cGAS to DNA also inhibits the cGAS activation. Both mechanisms lead to the failure of cGAS binding with self-DNA and the formation of cGAS dimers for activation. (B) In nucleosome dependent way, the DNA binding site B of cGAS is blocked by interacting with the AP. The AP is formed by histones H2A and H2B. Interact with the AP is cGAS conserved amino acid residues R222 and R241. In this regard, the chromatin tethering could be altered by the methylation of cGAS by SUV39H1, competitive binding of MRN and accumulation of misprocessed linker-histone mRNAs, etc. The figures were created using scientific image and illustration software, BioRender (BioRender.com).