Brown K D, Ziv Y, Sadanandan S N, Chessa L, Collins F S, Shiloh Y, Tagle D A
Laboratory of Gene Transfer, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1840-5. doi: 10.1073/pnas.94.5.1840.
The product of the ataxia-telangiectasia gene (ATM) was identified by using an antiserum developed to a peptide corresponding to the deduced amino acid sequence. The ATM protein is a single, high-molecular weight protein predominantly confined to the nucleus of human fibroblasts, but is present in both nuclear and microsomal fractions from human lymphoblast cells and peripheral blood lymphocytes. ATM protein levels and localization remain constant throughout all stages of the cell cycle. Truncated ATM protein was not detected in lymphoblasts from ataxia-telangiectasia patients homozygous for mutations leading to premature protein termination. Exposure of normal human cells to gamma-irradiation and the radiomimetic drug neocarzinostatin had no effect on ATM protein levels, in contrast to a noted rise in p53 levels over the same time interval. These findings are consistent with a role for the ATM protein in ensuring the fidelity of DNA repair and cell cycle regulation following genome damage.
通过使用针对与推导的氨基酸序列相对应的肽段所制备的抗血清，鉴定出共济失调毛细血管扩张症基因（ATM）的产物。ATM蛋白是一种单一的高分子量蛋白，主要存在于人类成纤维细胞的细胞核中，但在人类淋巴母细胞和外周血淋巴细胞的细胞核及微粒体组分中均有存在。在细胞周期的所有阶段，ATM蛋白的水平和定位均保持恒定。在因突变导致蛋白过早终止而纯合的共济失调毛细血管扩张症患者的淋巴母细胞中，未检测到截短的ATM蛋白。与在相同时间间隔内p53水平显著升高形成对比的是，正常人细胞暴露于γ射线和放射模拟药物新制癌菌素后，ATM蛋白水平未受影响。这些发现与ATM蛋白在确保基因组损伤后DNA修复的保真度和细胞周期调控方面所起的作用相一致。
