Abstract
The initial step of the V(D)J recombination occurs through the generation of a DNA double-strand break (dsb). Defects in the DNA-dependent protein kinase complex (DNA-PK) result in an inability to perform either V(D)J recombination or any dsb repair effectively. The human autosomal T-B-severe combined immunodeficiency (SCID) condition is characterized by an absence of both B and T lymphocytes and is accompanied in some patients by an increase in gamma-ray sensitivity (T-B-RS SCID) comparable to that found in mouse SCID cells. We show here that cells from six patients with T-B-RS SCID had normal DNA-dsb repair kinetics. Furthermore, DNA-PK activity was present in extracts from these human T-B-RS SCID fibroblasts. We therefore conclude that some human T-B-RS SCID disorders are not caused by a defect in an essential DNA-PK component.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B-Lymphocytes / pathology
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Cells, Cultured
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DNA
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DNA Damage / radiation effects*
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DNA Repair / radiation effects*
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DNA-Activated Protein Kinase
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DNA-Binding Proteins*
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Electrophoresis, Gel, Pulsed-Field
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Enzyme Activation / genetics
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Enzyme Activation / radiation effects
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Fibroblasts / enzymology*
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Fibroblasts / radiation effects*
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Gamma Rays
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Humans
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Lymphopenia / genetics
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Lymphopenia / pathology
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Nuclear Proteins
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Protein Serine-Threonine Kinases / deficiency*
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Protein Serine-Threonine Kinases / genetics*
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Severe Combined Immunodeficiency / enzymology
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Severe Combined Immunodeficiency / genetics*
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Severe Combined Immunodeficiency / pathology
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T-Lymphocytes / pathology
Substances
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DNA-Binding Proteins
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Nuclear Proteins
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DNA
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DNA-Activated Protein Kinase
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PRKDC protein, human
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Protein Serine-Threonine Kinases