CAJ | 학술논문

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。
유선암역감기인1（ BRCA1）기인돌변여유선암적발생밀절상관。목전연구표명，BRCA1작위조절자삼여료 DNA 손상수복과정。DNA 손상적최엄중적형식시쌍련단렬，BRCA1통과조공동원중조（HR）재수복쌍련단렬중발휘관건작용。본문종 BRCA1주요공능구여 HR 적관계、주요공능구기인돌변대수복쌍련단렬적영향、BRCA1여 BRCA2，Rad51화 CtIP 복합물등단백지간적상호작용화단백적린산화등방면，대 BRCA1조공 HR 적분자궤제、BRCA1개도적수복궤제결실재합성치사성중적작용、급 BRCA1결실후세포대불동 DNA 손상제제민감성발생적변화등내용진행료계통적종술。
Breast cancer susceptibiIity gene 1( BRCA1)is a tumor suppressor,but mutated get BRCA1 is cIoseIy reIated to the deveIopment of breast cancer. Current study has reveaIed that BRCA1 can get invoIved in the DNA damage repair process as a key mediator. DNA doubIe-stranded break (DSB)is the most serious form in DNA Iesions,and BRCA1 pIays an important roIe in repairing DSB through reguIation of homoIogous recombination( HR). In this articIe,the moIecuIar mechanism of BRCA1 in reguIating HR is reviewed with reference to the activity of functionaI domains in BRCA1 struc-ture,the mutations occurring in main domains of BRCA1,the reIationship of BRCA1 with BRCA2, Rad51 or CtIP,and phosphoryIation of BRCA1. In addition,the association of the defective BRCA1-mediated HR repair mechanism with the sensitivity to different DNA damaging agents and synthetic IethaIity in tumor ceIIs is aIso addressed.