A DNA-sensing enzyme forms droplets that act as tiny bioreactors creating molecules to stimulate innate immunity - the body's first response to infection, University of Texas (UT) Southwestern researchers report. The work, published online on July 5, 2018 in Science, could lead to novel treatments for infections, autoimmune disease, and cancer. A hallmark of all three of those illnesses is the presence of DNA - either foreign or self - in the cell's gel-like interior known as the cytoplasm, said Dr. Zhijian "James" Chen, Professor of Molecular Biology at UT Southwestern, a Howard Hughes Medical Institute Investigator, and senior author of the study. The study's lead author is graduate student Mingjian Du. In 2012, Dr. Chen's laboratory discovered the enzyme cyclic GMP-AMP synthase (cGAS), which acts as a sensor in a cellular alarm system for innate immunity. The body has two immune systems. The first is an inborn, or innate, immune system that guards the body against threats it first encounters. The second is the adaptive immune system that deploys specialized immune cells to eradicate pathogens. The innate immunity sensor cGAS sounds the alarm when it encounters DNA - either from pathogens or from the body's own cells in the case of autoimmune disease - in areas of the cell where that genetic material should not be. Dr. Chen also identified the small molecule cGAMP, which is produced by the enzyme cGAS and functions as a secondary messenger that triggers innate immune responses. The current Science article is titled “DNA-Induced Liquid Phase Condensation of cGAS Activates Innate Immune Signaling.” The current study finds that when cGAS encounters pathogenic DNA, it binds with the DNA to create droplet-size, microreactors that hold together despite the lack of a membrane.
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