Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.
Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.
Trends Biochem Sci. 2021 Oct;46(10):822-831. doi: 10.1016/j.tibs.2021.05.011. Epub 2021 Jun 29.
Recognition of DNA is an evolutionarily highly conserved mechanism of immunity. In mammals, the cGAS-STING pathway plays a central role in coupling DNA sensing to the execution of innate immune mechanisms, both in contexts of infection as well as in noninfectious settings of cellular stress and injury. The indiscriminate ability of double-stranded DNA (dsDNA) to activate cGAS challenges our understanding on how engagement of this pathway is prevented on genomic self-DNA under homeostatic conditions. Here, we review recent discoveries on the regulation of cGAS on chromatin and we discuss implications for cGAS-dependent inflammatory phenotypes. We close by highlighting emerging developments on the role of nuclear cGAS and related open questions for future research.
DNA 识别是一种进化上高度保守的免疫机制。在哺乳动物中，cGAS-STING 途径在将 DNA 感应与先天免疫机制的执行联系起来方面发挥着核心作用，无论是在感染的情况下还是在细胞应激和损伤的非感染性环境中。双链 DNA（dsDNA）激活 cGAS 的无差别能力挑战了我们对在稳态条件下基因组自身 DNA 上如何防止这种途径结合的理解。在这里，我们回顾了 cGAS 在染色质上的调控的最新发现，并讨论了其对 cGAS 依赖性炎症表型的影响。最后，我们强调了核 cGAS 作用的新进展以及未来研究的相关问题。
