Foreign vs own DNA: How an innate immune sensor tells the difference

Scientists at EPFL and the Friedrich Miescher Institute have used cryo-electron microscopy to explain how a DNA-sensing biomolecule that is key to our innate immunity response is inactivated when it comes in contact with the cell's own DNA. A biomolecule that gained considerable attention over the past few years is cGAS, a "DNA sensor" that is involved in kickstarting immune responses in the body. Specifically, when a pathogen is infecting a cell, cGAS senses its DNA and begins a cascade of biochemical reactions that activate the body's so-called "innate" immune system - the first-line-of-defense part of our immune system. One of the main scientific mysteries surrounding cGAS has been how it can distinguish selffrom non-self DNA. But even more perplexing is the fact that cGAS also exists inside the cell's nucleus, where all the genetic material is stored. Now, scientists at EPFL and the Friedrich Miescher Institute in Switzerland have revealed an intriguing mechanism on how nucleosomes - the building units that package DNA inside the nucleus - bind and inactivate cGAS. Published in Nature , the collaborative work was led by EPFL Professor Andrea Ablasser and FMI scientist Nicolas Thomä, and provides new insights into the biology of this immunity-crucial molecule.