Atomic-Level Snapshots Show How Human DNA Repair Enzyme SMUG1 Works

Scientists have produced the first atomic-level images of the human DNA repair enzyme SMUG1, revealing how it recognizes and removes damaged bases such as uracil and 5-fluorouracil. By capturing SMUG1 in multiple states—alone, bound to uracil or 5-fluorouracil, and attached to double-stranded DNA—using a rare combined neutron–X-ray approach, the study maps active-site proton positions and hydrogen-bond networks. These insights advance understanding of DNA repair and could guide the design of drugs targeting SMUG1, with implications for cancer biology and leveraging Sweden’s new European Spallation Source neutron capabilities.