Abstract
V(D)J recombination generates a diverse array of antigen-binding specificities, but breakage and re-joining of DNA segments have grave implications for the maintenance of genomic stability and oncogenic risk. Exposure of eukaryotic cells to genotoxic agents activates a DNA damage checkpoint that induces cell-cycle arrest and DNA repair, or apoptosis. We discuss several lines of evidence implicating DNA-dependent protein kinase (DNA-PK), and the gene mutated in ataxia telangiectasia (ATM), two mammalian homologues of yeast DNA damage-checkpoint genes, in regulating the response to intrinsic DNA damage that occurs during V(D)J recombination.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, Nuclear*
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Ataxia Telangiectasia / genetics
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Cell Cycle
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DNA Damage*
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DNA Helicases*
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DNA-Activated Protein Kinase
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DNA-Binding Proteins / genetics
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Hematopoietic Stem Cells / immunology
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Humans
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Ku Autoantigen
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Lymphocytes / immunology*
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Molecular Sequence Data
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Mutation
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Nuclear Proteins / genetics
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Phenotype
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Protein Serine-Threonine Kinases / genetics
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Receptors, Antigen / genetics*
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Recombination, Genetic*
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Saccharomyces cerevisiae Proteins*
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Severe Combined Immunodeficiency / genetics
Substances
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Antigens, Nuclear
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DNA-Binding Proteins
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Nuclear Proteins
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Receptors, Antigen
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Saccharomyces cerevisiae Proteins
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high affinity DNA-binding factor, S cerevisiae
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DNA-Activated Protein Kinase
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PRKDC protein, human
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Protein Serine-Threonine Kinases
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DNA Helicases
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XRCC5 protein, human
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Xrcc6 protein, human
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Ku Autoantigen