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作 者:卢向阳[1] 田云[1] 周海燕[1] 彭丽莎[1] 徐锋[1]
机构地区:[1]湖南农业大学生化与发酵工程实验室,湖南省长沙市410128
出 处:《中国临床康复》2004年第29期6536-6537,i008,共3页Chinese Journal of Clinical Rehabilitation
摘 要:背景:乳腺癌易感蛋白2(breastcancersusceptibilityprotein2,BRCA2)是由乳腺癌易感基因2编码的一种在维持哺乳动物细胞染色体稳定及DNA损伤生物应答中发挥重要作用的肿瘤抑制因子。许多研究表明:BRCA2蛋白与遗传性乳腺癌、卵巢癌及范康尼氏贫血症的发生具有密切关系,猜测其与双链DNA损伤修复有关,但具体作用模型与机制仍不清楚。目的:回顾关于BRCA2蛋白结构与DNA损伤修复的研究,明确BRCA2蛋白在双链DNA损伤修复中的作用机制。研究选择:选择关于BRCA2蛋白及DNA损伤修复的文献。数据来源:进行全面的检索,检索手段包括电子检索、手工检索及个人通信等。数据提取:对检索到的BRCA2蛋白及DNA损伤修复的相关研究文章信息进行综述。主要观察指标:BRCA2蛋白的结构及其在DNA损伤修复中的作用模型与机制。结果:BRCA2蛋白在肿瘤抑制过程中行使重要功能,其C末端DBD中的DNA结合活性与BRC模体中的RAD51蛋白结合活性在双链DNA损伤修复的同源重组过程中起着直接作用。结论:BRCA2蛋白在双链DNA损伤修复中发挥重要作用,但其具体过程与整个信号通路仍需进一步研究证实,其有望开发为治疗与DNA损伤相关疾病的新靶点,为其预防康复提供理论依据。BACKGROUND:Breast cancer susceptibility protein BRCA 2 encoded by BRCA2 gene is a tumor suppressor required for maintenance of chromosomal stability in mammalian cells and playing a pivotal role in biological response to DNA damage. Many researches showed that BRCA2 protein was closely related to the pathogenesis of hereditary breast cancer, ovarian cancer and Fanconi anemia (FA), presumably involving DNA double stranded break (DSB) repair, but the exact mechanism of its actions remains unknown. OBJECTIVE:To review the researches on BRCA2 protein structure and DNA repair so as to elucidate the mechanism of BRCA2 in DNA repair. STUDY SELECTION:The documents about BRCA2 protein and DNA repair were chosen. DATA SOURCES:The data were searched overall including electronic search, craft search and personal communication search and so on.DATA EXTRATION: The information about BRCA2 protein and DNA repair in the researched documents was surveyed. MAIN OUTCOME MEASURES:The structure, function model and mechanism of BRCA2 protein in DNA repair are explored. RESULTS:The results showed that BRCA2 protein performed important functions in tumor suppression. The DNA)binding activities of DNA binding domain(DBD) of BRCA2,in conjunction with the RAD51 binding activities of the BRC repeat, were directly associated with DSB repair during homologous recombination. CONCLUSION:BRCA2 protein plays an important role in DSB repair, but the exact process and signal transduction pathway still need further study. The study of BRCA2 may hold significant value in developing new treatment target for diseases involving DNA damage.
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