乳腺癌易感基因1在DNA损伤修复中作用的研究进展  

Progress in role of breast cancer susceptibility gene 1 in DNA damage repair

作　　者：赵锡鹏[1] 张凤梅[1] 凤志慧[1] 

机构地区：[1]山东大学公共卫生学院环境与健康系,山东济南250012

出　　处：《中国药理学与毒理学杂志》2014年第4期606-611,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金项目(81172527);山东省科技发展计划(2013GGE27052);山东大学自主创新项目(2010TB017)~~

摘　　要：乳腺癌易感基因1(BRCA1)基因突变与乳腺癌的发生密切相关。目前研究表明,BRCA1作为调节者参与了DNA损伤修复过程。DNA损伤的最严重的形式是双链断裂,BRCA1通过调控同源重组(HR)在修复双链断裂中发挥关键作用。本文从BRCA1主要功能区与HR的关系、主要功能区基因突变对修复双链断裂的影响、BRCA1与BRCA2,Rad51和CtIP复合物等蛋白之间的相互作用和蛋白的磷酸化等方面,对BRCA1调控HR的分子机制、BRCA1介导的修复机制缺失在合成致死性中的作用、及BRCA1缺失后细胞对不同DNA损伤制剂敏感性发生的变化等内容进行了系统的综述。Breast cancer susceptibility gene 1 （BRCA1） is a tumor suppressor, but mutated get BRCA1 is closely related to the development of breast cancer. Current study has revealed that BRCA1 can get involved in the DNA damage repair process as a key mediator. DNA double-stranded break （DSB） is the most serious form in DNA lesions, and BRCA1 plays an important role in repairing DSB through regulation of homologous recombination （HR）. In this article, the molecular mechanism of BRCA1 in regulating HR is reviewed with reference to the activity of functional domains in BRCA1 struc- ture, the mutations occurring in main domains of BRCA1, the relationship of BRCA1 with BRCA2, Rad51 or CtlP, and phosphorylation of BRCAI. In addition, the association of the defective BRCA1- mediated HR repair mechanism with the sensitivity to different DNA damaging agents and synthetic lethality in tumor cells is also addressed.

关 键 词：乳腺癌易感基因1 DNA损伤 DNA修复 DNA断裂 双链 重组 遗传 

分 类 号：R737.9[医药卫生—肿瘤]