Cells need to distinguish between their own DNA and that of viruses. To solve this problem, plant, fungal and animal cells store their DNA in the nucleus, and respond to DNA in the cytoplasm by activating an inflammatory response. However, under certain abnormal circumstances, host-cell DNA can also accumulate in the cytoplasm, triggering inappropriate inflammation. In
a paper in Nature, Coquel
et al.
1 define a role for the protein SAMHD1 in preventing this cytoplasmic host-DNA build-up. The authors’ findings have implications for immune disease and cancer.
SAMHD1 is a nuclear protein that chemically inactivates nucleotides
2, preventing them from being used to build DNA. Inherited SAMHD1 mutations cause the rare inflammatory disorder Aicardi–Goutières syndrome, which involves increased production of proteins called interferons that activate the immune system. Under normal circumstances, interferons are produced only in response to infection, and help to fight off viruses
3.
