title: Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha.
abstract: Cells from patients with ataxia telangiectasia (AT) are hypersensitive to ionizing radiation and are defective in the regulation of DNA synthesis. A complementary DNA that corrects the radiation sensitivity and DNA synthesis defects in fibroblasts from an AT group D patient was isolated by expression cloning and shown to encode a truncated form of I kappa B-alpha, an inhibitor of the nuclear factor kappa B (NF-kappa B) transcriptional activator. The parental AT fibroblasts expressed large amounts of the I kappa B-alpha transcript and showed constitutive activation of NF-kappa B. The AT fibroblasts transfected with the truncated I kappa B-alpha expressed normal amounts of the I kappa B-alpha transcript and showed regulated activation of NF-kappa B. These results suggest that aberrant regulation of NF-kappa B and I kappa B-alpha contribute to the cellular defect in AT.
authors.affiliation: Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Dritschilo
mesh_terms: D000595:Amino Acid Sequence; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D005816:Genetic Complementation Test; D006801:Humans; D020672:I-kappa B Proteins; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011836:Radiation Tolerance; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA