Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks.
The Ku autoantigen is a well-characterized heterodimer of 70 and 86 kDa that binds to DNA ends, but its cellular function has been obscure. An electrophoretic mobility-shift assay and Ku antisera were used to show that Ku or a closely related protein was deficient in three mutant hamster cell lines from x-ray-sensitive complementation group 5, which is characterized by defects in DNA double-strand break repair and V(D)J recombination. Furthermore, Ku protein expression was restored when the cells reverted to x-ray resistance. The Ku p86 gene maps to human chromosome 2q33-35, and group 5 cells are rescued by almost precisely the same region, 2q34-36. Thus, biochemical and genetic evidence suggests that Ku is involved in pathways for DNA recombination and repair. By its association with a DNA-dependent protein kinase activated by DNA ends, Ku may also initiate a signaling pathway induced by DNA damage, perhaps for cell cycle arrest.
Rathmell
W K
WK
Department of Medicine, Stanford University School of Medicine, CA 94305.
Chu
G
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D000818:Animals; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002889:Chromosomes, Human, Pair 2; D006224:Cricetinae; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011836:Radiation Tolerance; D011995:Recombination, Genetic; D014965:X-Rays
D034961:Antigens, Nuclear; D001324:Autoantigens; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen