W. Rathmell
Last active: 8/8/2016

Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks.

Rathmell WK, Chu G
Proc Natl Acad Sci U S A. 1994 91 (16): 7623-7

PMID: 8052631 · PMCID: PMC44454 · DOI:10.1073/pnas.91.16.7623

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.

MeSH Terms (16)

Animals Antigens, Nuclear Autoantigens Cells, Cultured Chromosomes, Human, Pair 2 Cricetinae DNA-Binding Proteins DNA Damage DNA Helicases DNA Repair Humans Ku Autoantigen Nuclear Proteins Radiation Tolerance Recombination, Genetic X-Rays

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