Cut-and-Run: A New Mechanism by which V(D)J Recombination causes Genome Instability

V(D)J recombination errors have long been linked with chromosome alterations in lymphoid cancers. Here, we show that the recombination by-product complexes with the RAG recombinase to trigger DNA breaks throughout the genome in a reaction named cut-and-run. Following cutting, the broken DNA is released, providing substrates for chromosome translocations. Consistent with this, the breaks co-localise with those previously mapped in acute lymphoblastic leukaemia. We propose that cut-and-run is a new mechanism by which aberrant V(D)J recombination leads to genome instability.