Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway.

Two major DNA repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination (HR), repair double-stranded DNA breaks (DSBs) in all eukaryotes. Additionally, several alternative end-joining pathways (or subpathways) have been reported that characteristically use short-sequence homologies at the DNA ends to facilitate joining. How a cell chooses which DNA repair pathway to use (at any particular DSB) is a central and largely unanswered question. For one type of DSB, there is apparently no choice. DSBs mediated by the lymphocyte-specific recombination activating gene (RAG) endonuclease are repaired virtually exclusively by NHEJ. Here we demonstrate that non-RAG-mediated DSBs can be similarly forced into the NHEJ pathway by physical association with the RAG endonuclease.