LACK OF DETECTABLE DEFECT IN DNA DOUBLE-STRAND BREAK REPAIR AND DNA-DEPENDENT PROTEIN-KINASE ACTIVITY IN RADIOSENSITIVE HUMAN SEVERE COMBINED IMMUNODEFICIENCY FIBROBLASTS

The initial step of the V(D)J recombination occurs through the generat ion of a DNA double-strand break (dsb). Defects in the DNA-dependent p rotein kinase complex (DNA-PK) result in an inability to perform eithe r V(D)J recombination or any dsb repair effectively The human autosoma l T-B-severe combined immunodeficiency (SCID) condition is characteriz ed by an absence of both B and T lymphocytes and is accompanied in som e patients by an increase in gamma-ray sensitivity (T-B-RS SCID) compa rable 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. Furt hermore, 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 .