A family of eukaryotic protein kinases, the phosphatidylinositol 3-kinase-related kinases (PIKKs), has key functions in DNA repair and nutrient sensing. In humans, ATR kinase locates DNA damage through its partner, ATRIP. Once activated, ATR initiates a cell-cycle cascade that culminates in cell-cycle arrest. Wang et al. determined the high-resolution structure of Mec1-Ddc2 (the yeast homolog of ATR-ATRIP) by electron microscopy. The structure shows the detailed architecture of the multidomain complex that overall forms a dimer of heterodimers. The detailed analysis of the structure reveals how an allosteric mechanism may activate the kinase.