Rag mutations reveal robust alternative end joining. Corneo, B., Wendland, R. L., Deriano, L., Cui, X., Klein, I. A., Wong, S., Arnal, S., Holub, A. J., Weller, G. R., Pancake, B. A., Shah, S., Brandt, V. L., Meek, K., & Roth, D. B. Nature, 449(7161):483–486, September, 2007. doi abstract bibtex Mammalian cells repair DNA double-strand breaks (DSBs) through either homologous recombination or non-homologous end joining (NHEJ). V(D)J recombination, a cut-and-paste mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient. Nevertheless, DSB repair is not eliminated entirely in these animals: evidence of a third mechanism, 'alternative NHEJ', appears in the form of extremely rare V(D)J junctions and a higher rate of chromosomal translocations. The paucity of these V(D)J events has suggested that alternative NHEJ contributes little to a cell's overall repair capacity, being operative only (and inefficiently) when classical NHEJ fails. Here we find that removing certain portions of murine Rag proteins reveals robust alternative NHEJ activity in NHEJ-deficient cells and some alternative joining activity even in wild-type cells. We propose a two-tier model in which the Rag proteins collaborate with NHEJ factors to preserve genomic integrity during V(D)J recombination.
@article{corneo_rag_2007,
title = {Rag mutations reveal robust alternative end joining},
volume = {449},
issn = {1476-4687},
doi = {10.1038/nature06168},
abstract = {Mammalian cells repair DNA double-strand breaks (DSBs) through either homologous recombination or non-homologous end joining (NHEJ). V(D)J recombination, a cut-and-paste mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient. Nevertheless, DSB repair is not eliminated entirely in these animals: evidence of a third mechanism, 'alternative NHEJ', appears in the form of extremely rare V(D)J junctions and a higher rate of chromosomal translocations. The paucity of these V(D)J events has suggested that alternative NHEJ contributes little to a cell's overall repair capacity, being operative only (and inefficiently) when classical NHEJ fails. Here we find that removing certain portions of murine Rag proteins reveals robust alternative NHEJ activity in NHEJ-deficient cells and some alternative joining activity even in wild-type cells. We propose a two-tier model in which the Rag proteins collaborate with NHEJ factors to preserve genomic integrity during V(D)J recombination.},
language = {eng},
number = {7161},
journal = {Nature},
author = {Corneo, Barbara and Wendland, Rebecca L. and Deriano, Ludovic and Cui, Xiaoping and Klein, Isaac A. and Wong, Serre-Yu and Arnal, Suzzette and Holub, Abigail J. and Weller, Geoffrey R. and Pancake, Bette A. and Shah, Sundeep and Brandt, Vicky L. and Meek, Katheryn and Roth, David B.},
month = sep,
year = {2007},
keywords = {Animals, DNA-Binding Proteins, Homeodomain Proteins, Mice, Models, Genetic, Mutation, Recombination, Genetic},
pages = {483--486},
}
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Nevertheless, DSB repair is not eliminated entirely in these animals: evidence of a third mechanism, 'alternative NHEJ', appears in the form of extremely rare V(D)J junctions and a higher rate of chromosomal translocations. The paucity of these V(D)J events has suggested that alternative NHEJ contributes little to a cell's overall repair capacity, being operative only (and inefficiently) when classical NHEJ fails. Here we find that removing certain portions of murine Rag proteins reveals robust alternative NHEJ activity in NHEJ-deficient cells and some alternative joining activity even in wild-type cells. 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V(D)J recombination, a cut-and-paste mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient. Nevertheless, DSB repair is not eliminated entirely in these animals: evidence of a third mechanism, 'alternative NHEJ', appears in the form of extremely rare V(D)J junctions and a higher rate of chromosomal translocations. The paucity of these V(D)J events has suggested that alternative NHEJ contributes little to a cell's overall repair capacity, being operative only (and inefficiently) when classical NHEJ fails. Here we find that removing certain portions of murine Rag proteins reveals robust alternative NHEJ activity in NHEJ-deficient cells and some alternative joining activity even in wild-type cells. 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B."],"key":"corneo_rag_2007","id":"corneo_rag_2007","bibbaseid":"corneo-wendland-deriano-cui-klein-wong-arnal-holub-etal-ragmutationsrevealrobustalternativeendjoining-2007","role":"author","urls":{},"keyword":["Animals","DNA-Binding Proteins","Homeodomain Proteins","Mice","Models","Genetic","Mutation","Recombination","Genetic"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/zotero/tplas","dataSources":["YLgywGcXWx96vKKaB"],"keywords":["animals","dna-binding proteins","homeodomain proteins","mice","models","genetic","mutation","recombination","genetic"],"search_terms":["rag","mutations","reveal","robust","alternative","end","joining","corneo","wendland","deriano","cui","klein","wong","arnal","holub","weller","pancake","shah","brandt","meek","roth"],"title":"Rag mutations reveal robust alternative end joining","year":2007}