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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Nuclear / genetics
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Antigens, Nuclear / metabolism*
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Base Sequence
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DNA Breaks, Double-Stranded
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / physiology
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Genes, Reporter
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Ku Autoantigen
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Mice
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Recombination, Genetic*
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Sequence Homology, Nucleic Acid
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Translocation, Genetic*
Substances
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Antigens, Nuclear
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DNA-Binding Proteins
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Homeodomain Proteins
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RAG-1 protein
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Xrcc6 protein, mouse
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Ku Autoantigen