Wang, J. L. et al. Nat. Struct. Mol. Biol. 6, 482–487 (2018).

Repair of DNA double-strand breaks by nonhomologous end joining (NHEJ) is a complex process involving multiple proteins. Although the mechanism is generally understood, crucial insights into the kinetics of NHEJ complex assembly and disassembly have been lacking. Wang et al. devised a single-molecule method to analyze the process with finer detail. Their approach, which they call ‘DNA molecular forceps’, utilizes a construct that consists of two dsDNA segments connected by a third, bridging dsDNA segment. The construct is anchored to a surface at one end and attached to a magnetic bead at the other end; a magnet generates an extension force on the construct. When NHEJ protein components bind to the construct, the free ends of the two dsDNA segments are joined together, resulting in a reduction in overall construct length. The system allowed Wang et al. to carefully dissect the NHEJ process and propose a detailed model for DNA double-strand break repair by NHEJ. AD