Lee Joo-Hyeon, Lim Dae-Sik
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Guseong-D, Yuseong-G, Daejeon.
FEBS J. 2006 Apr;273(8):1630-6. doi: 10.1111/j.1742-4658.2006.05191.x.
The Nbs1 protein associates with Mre11 and Rad50 proteins to form the Mre11-Rad50-Nbs1 complex, which plays an important role in the intracellular signaling pathway activated in response to DNA damage. Mutations in the genes for each of these three components of the Mre11-Rad50-Nbs1 complex result in human diseases characterized by genomic instability. Insight into the functions of Nbs1 in the DNA damage response mediated by the protein kinase, ataxia telangiectasia mutated, has been provided by recent studies. Nbs1 acts both as a downstream target of ataxia telangiectasia mutated in the S-phase checkpoint of the cell cycle as well as an upstream modulator or activator of ataxia telangiectasia mutated in the DNA damage response.
Nbs1蛋白与Mre11和Rad50蛋白结合形成Mre11-Rad50-Nbs1复合物，该复合物在响应DNA损伤而激活的细胞内信号通路中起重要作用。Mre11-Rad50-Nbs1复合物这三个组分各自的基因突变会导致以基因组不稳定为特征的人类疾病。最近的研究揭示了Nbs1在由蛋白激酶共济失调毛细血管扩张突变体介导的DNA损伤反应中的功能。Nbs1在细胞周期的S期检查点中作为共济失调毛细血管扩张突变体的下游靶点，同时在DNA损伤反应中作为共济失调毛细血管扩张突变体的上游调节剂或激活剂发挥作用。
