Abstract
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.
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Acknowledgements
We thank M. Leversha at the Memorial Sloan-Kettering Cancer Centre, Molecular Cytogenetics Core Facility for performing the FISH analysis, and B. Elliott, J. Stark, V. Lee and members of the Jasin laboratory for helpful discussions. D.M.W. was supported by the Leukemia and Lymphoma Society (5415-05) and a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund. This work was supported by the Lehman Brothers Foundation and National Institutes of Health (NIH) R0154688 (M.J.).
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Weinstock, D., Brunet, E. & Jasin, M. Formation of NHEJ-derived reciprocal chromosomal translocations does not require Ku70. Nat Cell Biol 9, 978–981 (2007). https://doi.org/10.1038/ncb1624
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DOI: https://doi.org/10.1038/ncb1624
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