A new study links DNA damage sensors with the type I interferon (IFN) response to cytosolic DNA. Stimulator of IFN genes (STING) is an endoplasmic reticulum (ER)-residing protein that promotes IFN signalling downstream of cytosolic nucleic acid sensors. Kondo et al. observed that cytoplasmic MRE11 (together with its binding partner RAD50) is essential for STING translocation from the ER to the Golgi apparatus and for interferon regulatory factor 3 phosphorylation in response to cytosolic double-stranded DNA (dsDNA). Cytoplasmic MRE11 seems to sense dsDNA through interactions with the sugar–phosphate DNA backbone, whereas its nuclease activity prevents excessive IFN production, probably by subsequently cleaving the MRE11-bound DNA. As it was dispensable for IFN expression downstream of herpes simplex virus and Listeria monocytogenes, the authors suggest that MRE11 may initiate a type I IFN response downstream of cell-intrinsic damage.