Liquid droplets step on the cGAS Spontaneous partitioning of a homogeneous solution of molecules, or liquid-phase separation, underlies the formation of cellular bodies from P granules to nucleoli. Essentially, dense-phase liquid droplets act like cellular compartments. Du and Chen show that DNA binding to its cytoplasmic sensor, cyclic GMP–AMP synthase (cGAS), results in liquid droplets containing activated cGAS (see the Perspective by Ablasser). This phenomenon occurs through multivalent interactions, augmented by zinc, between DNA binding domains on cGAS and DNA in a length-dependent manner. Binding triggers a switchlike reaction that concentrates the enzyme and reactants to enhance STING-dependent interferon responses. Science, this issue p. 704; see also p. 646 DNA sensor cGAS forms liquid droplets that stimulate innate immune responses. The binding of DNA to cyclic GMP–AMP synthase (cGAS) leads to the production of the secondary messenger cyclic GMP–AMP (cGAMP), which activates innate immune responses. We have shown that DNA binding to cGAS robustly induced the formation of liquidlike droplets in which cGAS was activated. The disordered and positively charged cGAS N terminus enhanced cGAS-DNA phase separation by increasing the valencies of DNA binding. Long DNA was more efficient in promoting cGAS liquid phase separation and cGAS enzyme activity than short DNA. Moreover, free zinc ions enhanced cGAS enzyme activity both in vitro and in cells by promoting cGAS-DNA phase separation. These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling.

中文翻译：

---

DNA 诱导的 cGAS 液相缩合激活先天免疫信号

液滴踩在 cGAS 分子均匀溶液的自发分配或液相分离是从 P 颗粒到核仁的细胞体形成的基础。本质上，密相液滴就像细胞隔室一样。Du 和 Chen 表明，DNA 与其细胞质感受器环状 GMP–AMP 合酶 (cGAS) 结合会产生含有活化 cGAS 的液滴（参见 Ablasser 的观点）。这种现象是通过 cGAS 和 DNA 上的 DNA 结合域之间以长度依赖的方式通过锌增强的多价相互作用发生的。结合会触发开关样反应，该反应会浓缩酶和反应物以增强 STING 依赖性干扰素反应。科学，这个问题 p。704; 另见 p. 646 DNA 传感器 cGAS 形成可刺激先天免疫反应的液滴。DNA 与环 GMP-AMP 合酶 (cGAS) 的结合导致产生第二信使环 GMP-AMP (cGAMP)，从而激活先天免疫反应。我们已经表明，与 cGAS 结合的 DNA 强烈诱导了 cGAS 被激活的液状液滴的形成。无序且带正电荷的 cGAS N 末端通过增加 DNA 结合的价态来增强 cGAS-DNA 相分离。长DNA比短DNA更有效地促进cGAS液相分离和cGAS酶活性。此外，游离锌离子通过促进 cGAS-DNA 相分离增强 cGAS 酶在体外和细胞内的活性。这些结果表明，DNA 诱导的 cGAS 相变促进了 cGAMP 的产生和先天免疫信号传导。