Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, USA.
Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, USA.
Trends Cell Biol. 2020 Aug;30(8):594-605. doi: 10.1016/j.tcb.2020.05.006. Epub 2020 Jun 13.
Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a major responder to the pathogenic DNA of viruses and bacteria. Upon DNA binding, cGAS becomes enzymatically active to generate the second messenger cGAMP, leading to activation of inflammatory genes, type I interferon production, autophagy, and cell death. Following genotoxic stress, cGAS can also respond to endogenous DNA, deriving from mitochondria, endogenous retroelements, and chromosomes to affect cellular signaling, secretion, and cell fate decisions. However, under unperturbed conditions, signaling from self-DNA is largely, but not completely, inhibited. Here we review how endogenous DNA is exposed to cGAS, how signaling is attenuated but activated under pathological conditions, and how low-level signaling under unperturbed conditions might prime antipathogenic responses.
环鸟苷酸-腺苷酸合成酶（cGAS）是病毒和细菌致病性 DNA 的主要应答者。cGAS 与 DNA 结合后，酶活性被激活，生成第二信使 cGAMP，导致炎症基因激活、Ⅰ型干扰素产生、自噬和细胞死亡。在遗传毒性应激后，cGAS 还可以对来自线粒体、内源性逆转录元件和染色体的内源性 DNA 作出反应，影响细胞信号转导、分泌和细胞命运决定。然而，在未受干扰的情况下，来自自身 DNA 的信号受到很大但并非完全抑制。本文综述了内源性 DNA 如何暴露于 cGAS，信号在病理条件下如何被减弱但又被激活，以及未受干扰情况下的低水平信号如何为抗病原体反应做好准备。
