title: Lack of detectable defect in DNA double-strand break repair and DNA-dependent protein kinase activity in radiosensitive human severe combined immunodeficiency fibroblasts.
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.
authors.affiliation: INSERM U429, Développement Normal et Pathologique du Système Immunitaire, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Nicolas
authors.forename: N J
authors.initials: NJ
authors.lastname: Finnie
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: D
authors.initials: D
authors.lastname: Papadopoulo
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: S P
authors.initials: SP
authors.lastname: Jackson
authors.forename: J P
authors.initials: JP
authors.lastname: de Villartay
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology; D002478:Cells, Cultured; D004247:DNA; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D016521:Electrophoresis, Gel, Pulsed-Field; D004789:Enzyme Activation / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000201:enzymology* / Q000528:radiation effects*; D005720:Gamma Rays; D006801:Humans; D008231:Lymphopenia / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases