Formation of NHEJ-derived reciprocal chromosomal translocations does not require Ku70

Chromosomal translocations in lymphoid tumours can involve antigen-receptor loci undergoing V(D)J recombination. Here, we show that translocations are recovered from the joining of RAG-generated double-strand breaks (DSBs) on one chromosome to an endonuclease-generated DSB on a second chromosome, providing evidence for the participation of non-RAG DSBs in some lymphoid translocations. Surprisingly, translocations are increased in cells deficient for the nonhomologous end-joining (NHEJ) protein Ku70, implicating non-canonical joining pathways in their etiology.