Brown K D, Lataxes T A, Shangary S, Mannino J L, Giardina J F, Chen J, Baskaran R
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA.
J Biol Chem. 2000 Mar 3;275(9):6651-6. doi: 10.1074/jbc.275.9.6651.
Genome damaging events, such as gamma-irradiation exposure, result in the induction of pathways that activate DNA repair mechanisms, halt cell cycle progression, and/or trigger apoptosis. We have investigated the effects of gamma-irradiation on cellular levels of the Ku autoantigens. Ku70 and Ku80 have been shown to form a heterodimeric complex that can bind tightly to free DNA ends and activate the protein kinase DNA-PKcs. We have found that irradiation results in an up-regulation of cellular levels of Ku70, but not Ku80, and that this enhanced level of Ku70 accumulates within the nucleus. Further, we uncovered that the postirradiation up-regulation of Ku70 utilizes a mechanism that is dependent on both p53 and damage response protein kinase ATM (ataxia-telangiectasia-mutated); however, the activation of DNA-PK does not require Ku70 up-regulation. These findings suggest that Ku70 up-regulation provides the cell with a means of assuring either proper DNA repair or an appropriate response to DNA damage independent of DNA-PKcs activation.
基因组损伤事件，如γ射线照射，会导致激活DNA修复机制、使细胞周期进程停滞和/或触发细胞凋亡的信号通路的诱导。我们研究了γ射线照射对Ku自身抗原细胞水平的影响。Ku70和Ku80已被证明能形成异源二聚体复合物，该复合物可紧密结合游离DNA末端并激活蛋白激酶DNA-PKcs。我们发现，照射导致Ku70而非Ku80的细胞水平上调，且这种增强的Ku70水平在细胞核内积累。此外，我们发现照射后Ku70的上调利用了一种依赖于p53和损伤反应蛋白激酶ATM（共济失调毛细血管扩张症突变型）的机制；然而，DNA-PK的激活并不需要Ku70上调。这些发现表明，Ku70上调为细胞提供了一种确保正确DNA修复或对DNA损伤做出适当反应的方式，而与DNA-PKcs激活无关。
