MRE11-RAD50-NBS1复合物的功能与人类疾病的研究进展  

Research Progress in the Roles of MRE11-RAD50-NBS1 Complex and Human Diseases

作　　者：许晓慧 刘一丹 XU Xiaohui;LIU Yidan(Women’s Hospital,School of Medicine,Zhejiang University,Hangzhou 310006,China)

机构地区：[1]浙江大学医学院附属妇产科医院,杭州310006

出　　处：《中国医学科学院学报》2024年第2期232-241,共10页Acta Academiae Medicinae Sinicae

基　　金：浙江省自然科学基金项目(LY19C050002)。

摘　　要：生物体的DNA常遭受着来自体外和体内各种因素的攻击,其中DNA双链断裂(DSB)是严重的一种DNA损伤方式。为了保证遗传信息的稳定性,生物体自身存在应对DNA损伤的修复机制。同源重组修复是精确的修复DSB的方式,MRE11-RAD50-NBS1(MRN)复合物是参与同源重组修复的关键蛋白,在不同物种之间存在保守性。从前关于MRN复合物的功能研究主要来源于酿酒酵母和线虫等低等生物,近些年来对哺乳动物MRN复合物的研究提示MRN复合物在高等动物DNA损伤修复中存在功能。本文综述了MRN复合物的组成和结构及其在DNA损伤同源重组修复中的功能,同时也介绍了MRN复合物异常所带来的人类疾病共济失调性毛细血管扩张综合征类似病症、奈梅亨断裂综合征和奈梅亨断裂综合征类似病症,并对这3类DNA损伤修复缺陷疾病的临床表型和相关小鼠模型研究进行了总结。DNA is susceptible to various factors in vitro and in vivo and experience different forms of damage,among which double-strand break(DSB)is a deleterious form.To maintain the stability of genetic information,organisms have developed multiple mechanisms to repair DNA damage.Among these mechanisms,homologous recombination(HR)is praised for the high accuracy.The MRE11-RAD50-NBS1(MRN)complex plays an important role in HR and is conserved across different species.The knowledge on the MRN complex mainly came from the previous studies in Saccharomyces cerevisiae and Caenorhabditis elegans,while studies in the last decades have revealed the role of mammalian MRN complex in DNA repair of higher animals.In this review,we first introduces the MRN complex regarding the composition,structure,and roles in HR.In addition,we discuss the human diseases such as ataxia-telangiectasia-like disorder,Nijmegen breakage syndrome,and Nijmegen breakage syndrome-like disorder that are caused by dysfunctions in the MRN complex.Furthermore,we summarize the mouse models established to study the clinical phenotypes of the above diseases.

关 键 词：DNA损伤修复 DNA双链断裂 同源重组 MRE11-RAD50-NBS1复合物 

分 类 号：R34[医药卫生—基础医学]