PerspectiveImmunology

Phase separation focuses DNA sensing

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Science  17 Aug 2018:
Vol. 361, Issue 6403, pp. 646-647
DOI: 10.1126/science.aau6019

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Summary

The presence of any double-stranded DNA (dsDNA) in the cytosol is a potent trigger for the activation of innate immune responses. In the context of an infection, immunorecognition of “foreign” dsDNA serves as a central host strategy to detect the presence of pathogens. Under certain conditions, however, sensing of aberrant cytosolic self-dsDNA can also promote destructive inflammation in autoinflammatory diseases. A fundamental question is how cells spatially organize and biochemically regulate the recognition of intracellular dsDNA in the vast cytosolic space of a cell. On page 704 in this issue, Du and Chen (1) introduce an elegant explanation by demonstrating that phase separation of the dsDNA sensor cGAS [cyclic GMP (guanosine monophosphate)–AMP (adenosine monophosphate) synthase] enables this central task. This adds to the cellular processes that are facilitated by phase separation.