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Science 16 June 1995:
Vol. 268. no. 5217, pp. 1619 - 1621
DOI: 10.1126/science.7777860
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Articles

Science, Vol 268, Issue 5217, 1619-1621
Copyright © 1995 by American Association for the Advancement of Science

articles

Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha

M Jung, Y Zhang, S Lee, and A Dritschilo

Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC 20007, USA.

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.


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