Antigen receptor loci contain numerous gene segments that are recombined in response to antigen stimulation. The RAG endonuclease makes the double-strand breaks that initiate recombination. The ends of these breaks are hairpins that can only be cleaved by the Artemis nuclease. Here, it is shown that the specificity for Artemis is dictated by the histone protein H2AX, in cooperation with the repair protein MDC-1. In the absence of H2AX, another nuclease, CtIP, can open the ends but they are not joined efficiently; this leads to genomic instability.
- Beth A. Helmink
- Anthony T. Tubbs
- Barry P. Sleckman
