人类神经退行性疾病相关的三核苷酸重复DNA序列不稳定性机制研究进展  

Progress on the mechanistic research of the trinucleotide repeat instabilities underlying human neurodegenerative diseases

作　　者：吕柯孬 潘学峰[1,2,3] Kenao Lv;Xuefeng Pan(School of Life Science,Beijing Institute of Technology,Beijing 100081,China;School of Medicine,Hebei University,Baoding 071030,China;School of Chemistry and Enviromental Science,Hebei University,Baoding 071002,China)

机构地区：[1]北京理工大学生命学院,北京100081 [2]河北大学医学院,保定071030 [3]河北大学化学与环境科学学院,保定071002

出　　处：《遗传》2021年第9期835-848,共14页Hereditas（Beijing)

基　　金：北京市自然科学基金(No.5132014);河北省医学研究计划重点项目(No.20160051)资助。

摘　　要：三核苷酸重复DNA序列扩增或缺失不稳定性与50多种人类神经退行性疾病有关。与疾病相关的三核苷酸重复拷贝数的增加或减少,影响了特定基因的表达,或因之产生具有细胞毒性的RNA和蛋白质已成为相关疾病的共有病理机制。现有的研究表明,疾病相关的三核苷酸重复拷贝数的改变有可能起因于相关三核苷酸重复DNA序列的异常DNA复制、修复、重组以及基因转录。有关人类遗传学研究也提示,发生在疾病相关的三核苷酸重复DNA部位的异常DNA复制、修复、重组或基因转录确有可能在三核苷酸重复DNA不稳定过程中发挥着关键作用。本文根据本课题组的研究经验,综述了近年来有关疾病相关三核苷酸重复不稳定性机制的研究进展,包括碱基突变不稳定、重复单元的扩增和缺失不稳定,以助更好地理解疾病相关三核苷酸重复DNA序列不稳定性的分子机制。The expansion and deletion instabilities shown by some trinucleotide repeated DNA sequences are associated with more than 50 neurodegenerative diseases in humans.The increase or decrease of the trinucleotide repeat units underlying the diseases are not yet clearly explained using any mechanism,but has been found to affect the expression of specific genes,or produces cytotoxic RNA and protein,which has now become a common pathological mechanism of the diseases.The ongoing studies have shown that the changes in the copy numbers of the disease-related trinucleotide repeats may result from abnormal DNA replication,repair,recombination,and gene transcription.Human genetical studies also suggest that abnormal DNA replication,repair,recombination,or gene transcription that occurred in the disease-related trinucleotide repeat DNA sites may play a key role in the trinucleotide repeat DNA instabilities.Based on the research experiences of our research group,this paper reviews the recent research progress on the mechanisms of the disease-associated trinucleotide repeat DNA instabilities including their base mutation instabilities,the amplification and deletion instabilities of the repeat units,to better understand the molecular mechanism of the disease-associated trinucleotide repeats instabilities.

关 键 词：三核苷酸重复 不稳定性扩增 R-环 非B型DNA二级结构 神经退行性疾病 

分 类 号：R741[医药卫生—神经病学与精神病学]