Rathmell W K, Chu G
Department of Medicine, Stanford University School of Medicine, CA 94305.
Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7623-7. 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.
Ku自身抗原是一种特征明确的由70 kDa和86 kDa组成的异二聚体，可与DNA末端结合，但其细胞功能一直不清楚。采用电泳迁移率变动分析和Ku抗血清表明，Ku或一种密切相关的蛋白质在来自X射线敏感互补组5的三个突变仓鼠细胞系中存在缺陷，该互补组的特征是DNA双链断裂修复和V(D)J重组存在缺陷。此外，当细胞恢复对X射线的抗性时，Ku蛋白表达得以恢复。Ku p86基因定位于人类染色体2q33 - 35，而5组细胞几乎被完全相同的区域2q34 - 36拯救。因此，生化和遗传学证据表明Ku参与了DNA重组和修复途径。通过与由DNA末端激活的DNA依赖性蛋白激酶结合，Ku也可能启动由DNA损伤诱导的信号通路，也许是用于细胞周期停滞。
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