在DNA损伤修复信号传导通路中ATM介导的BRCA1及RAD51作用机理的研究

冯爽; 曹建平; 朱巍; 宋建元; 李翀; 盛方军; 樊赛军; F. Eckardt-Schupp

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在DNA损伤修复信号传导通路中ATM介导的BRCA1及RAD51作用机理的研究

研究论文 | 更新时间：2023-03-30

- 在DNA损伤修复信号传导通路中ATM介导的BRCA1及RAD51作用机理的研究
- Mechanisms for ATM mediated downstream gene BRCA1 and RAD51 in signaling pathway of DNA injury repair
- 辐射研究与辐射工艺学报 2006年24卷第2期页码：115-119
- 作者机构：
  
  1.苏州大学放射医学与公共卫生学院　苏州　215123
  2.Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20057 USA
  3.GSF-National Research Center Institute of Radiobiology Germany
- 作者简介：
  
  冯爽，女，1977年6月出生，2001年毕业于苏州大学放射医学与公共卫生学院，现为2003级在读硕士研究生，放射医学专业，住院医师
  曹建平
- 基金信息：
  
  国家自然科学基金(30170288);江苏省普通高校自然科学基金重点项目(04KJA180121);苏州大学江苏省级重点实验室开放经费项目(KJS05029);苏州大学医学发展基金重点项目(EE126032)
- DOI：
  中图分类号：
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冯爽, 曹建平, 朱巍, 等. 在DNA损伤修复信号传导通路中ATM介导的BRCA1及RAD51作用机理的研究[J]. 辐射研究与辐射工艺学报, 2006,24(2):115-119.

FENG Shuang, CAO Jianping, ZHU Wei, et al. Mechanisms for ATM mediated downstream gene BRCA1 and RAD51 in signaling pathway of DNA injury repair[J]. Journal of Radiation Research and Radiation Processing, 2006,24(2):115-119.
冯爽, 曹建平, 朱巍, 等. 在DNA损伤修复信号传导通路中ATM介导的BRCA1及RAD51作用机理的研究[J]. 辐射研究与辐射工艺学报, 2006,24(2):115-119. DOI：

FENG Shuang, CAO Jianping, ZHU Wei, et al. Mechanisms for ATM mediated downstream gene BRCA1 and RAD51 in signaling pathway of DNA injury repair[J]. Journal of Radiation Research and Radiation Processing, 2006,24(2):115-119. DOI：

摘要

为阐明毛细血管扩张性共济失调突变基因（Ataxia telangiectasia mutated，ATM）介导的乳癌基因1 （Breast cancer gene 1，Brca1）磷酸化及其下游DNA修复相关蛋白（DNA damage repair protein 51，RAD51）在DNA损伤修复信号传导通路中作用机理，以源于正常人皮肤的成纤维细胞系GM细胞（Originated from human skin fibroblast GM Cell，GM0639）为对照，用免疫共沉淀与Western blot方法，观察,60,Co γ射线照射后共济失调症（Ataxia telangiectasia，AT）细胞、ATM转染的AT细胞（ATM,+,-AT）和GM细胞的BRCA1及RAD51蛋白表达的变化。经0、5、10、20Gy辐照后，AT细胞通过免疫共沉淀及Western Blot法分析其中ATM和BRCA1蛋白以及BRCA1和RAD51蛋白之间的相互作用以及PI3K抑制剂对ATM磷酸化其下游基因的影响。0Gy照射ATM,+,-AT和GM细胞未出现BRCA1表达条带；照射后，GM细胞、ATM细胞BRCA1和RAD51蛋白均有表达，而AT细胞无表达；PI3K抑制剂Wortmannin对经电离辐射照射后的AT、ATM,+,-AT和GM细胞中BRCA1蛋白表达具有抑制作用；照射后ATM,+,-AT和GM细胞中BRCA1和RAD51蛋白均有表达。因此，电离辐射照射后，BRCA1由ATM介导磷酸化后可进一步与RAD51相互作用，这是信号通路传导过程中的一个级联反映，从而修复损伤的DNA，保持基因组的稳定性。

Abstract

In order to investigate mechanisms of ATM (Ataxia telangiectasia mutated) genes mediating phosphorylation of BRCA1(breast cancer gene 1) and its downstream gene RAD51 (DNA damage repair protein 51) in signaling pathway of DNA injury repair, we applied immunocoprecipitate and Western blot to observe changes in the expressions of BRCA1 and RAD51 proteins in AT cells, ATM,+,-AT cells (AT cells transfected with ATM genes) and GM cells (originated from human skin fibroblast, GM 0639) and used as control, after 5, 10 and 20Gy ,60,Co γ-ray irradiation at dose rate of 1.0Gy/min. The irradiated AT cells were analyzed to study interactive action between ATM and BRCA1 protein, BRCA1 and RAD51 protein, and the effect of PI3K inhibitor on ATM phosphorylating, its downstream gene, by immunocoprecipitate and Western blot. No expression bands of BRCA1 were found in ATM,+,-AT and GM cells of the control. After the irradiation, the BRCA1 and RAD51 were both expressed in GM and ATM cells. The PI3K inhibitor Wortmannin could inhibit the expression of BRCA1 in the AT, ATM,+,-AT and GM cells. The BRCA1 and RAD proteins were both expressed in ATM,+,-AT cells and GM cells. Therefore, after the irradiation the phosphorylation of BRCA1 mediated by ATM could further interact with RAD51. This is a cascade in signaling pathway for DNA damage repair and genome stabilization.

关键词

毛细血管扩张性共济失调突变基因乳癌基因1DNA修复相关蛋白磷酸化

Keywords

Ataxia telangiectasia mutatedBreast cancer gene 1DNA damage repair protein 51Phosphorylation

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