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 kD a that binds to DNA ends, but its cellular function has been obscure. An electrophoretic mobility-shift assay and Ku antisera were used to s how that Ku or a closely related protein was deficient in three mutant hamster cell lines from x-ray-sensitive complementation group 5, whic h is characterized by defects in DNA double-strand break repair and V( D)J recombination. Furthermore, Ku protein expression was restored whe n the cells reverted to x-ray resistance. The Ku p86 gene maps to huma n chromosome 2q33-35, and group 5 cells are rescued by almost precisel y the same region, 2q34-36. Thus, biochemical and genetic evidence sug gests 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 dama ge, perhaps for cell cycle arrest.