摘要
R环是一种由RNA:DNA杂交体和一条DNA单链组成的三链核酸结构。R环可分为生理性和病理性两种类型。生理性R环参与DNA复制、转录和基因表达调控等多个生理学过程,而病理性R环则诱导产生DNA损伤和基因组重排。影响R环形成的因素有许多,不受调控的R环通过干扰DNA复制和双链DNA断裂修复等过程破坏基因组的稳定性,严重时可引发癌症。因此,对R环的调控至关重要。RNA/DNA解旋酶Senataxin(SETX),DEAD-box解旋酶5(DDX5),核糖核酸酶H(RNase H)和DNA拓扑异构酶Ⅰ(topoⅠ)等在调节体内R环平衡过程中发挥了重要作用。其中,SETX是最具特性的R环分解酶之一,能分解在转录终止位点、复制-转录冲突期间和DNA损伤修复过程中产生的R环。SETX突变将导致共济失调伴眼动失用症2型(AOA2)和肌萎缩性侧索硬化症4型(ALS4)。然而,随着对R环研究的深入,仍然存在许多尚未解决的问题。例如,对生理性和病理性R环的结构功能研究仍需深入探索。本文主要针对R环定义和分类、影响R环形成的因素、R环对基因组稳定性的影响和R环相关疾病进行阐述,探索未来将R环作为治疗靶点的可能性。
The R-loop is a three-stranded nucleic acid structure,which consists of a RNA:DNA hybrid and a DNA single strand.R-loop can be divided into two types:physiological and pathological.The physiological R-loop is involved in many physiological processes such as DNA replication,transcription,and gene expression regulation,while the pathological R-loop induces DNA damage and genome rearrangement.There are many factors that affect the formation of R-loops.Unregulated R-loops destroy genomic stability by interfering with DNA replication and double-strand DNA break repair,and can cause cancer.Therefore,the regulation of R-loops is very important.RNA/DNA helicase Senataxin(SETX),DEAD-box helicase 5(DDX5),ribonuclease H(RNase H)and DNA topoisomerase I(topoⅠ)play an important role in regulating the balance of R-loops in vivo.Among them,SETX is one of the most characteristic R-loop decomposing enzymes,which can dissolve the R-loops produced during transcriptional termination sites,replication-transcriptional conflicts and DNA damage repair.Senataxin mutations will lead to ataxia with eye movement apraxia type 2(AOA2)and amyotrophic lateral sclerosis type 4(ALS4).Currently there are still many unsolved issues,although many in-depth studies of R-loops have been car-ried out.Therefore,the structure and function of physiological and pathological R-loops still need to be further explored.This review mainly focuses on the definition and classification of R-loops,the factors that affect the formation of R-loops,the influence of R-loops on genomic stability and R-loop-related dis-eases,and explores the possibility of using R-loops as a therapeutic target in the future.
作者
徐图南
郭燕君
潘巍巍
XU Tu-Nan;GUO Yan-Jun;PAN Wei-Wei(College of Pharmaceutical Science,Zhejiang University of Technology,Hangzhou 310014,China;Department of Cell Biology,College of Medicine,Jiaxing University,Jiaxing 314001,Zhejiang,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2023年第9期1238-1246,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.31871402)
浙江省自然科学基金(No.LY17H160060)
浙江省鲲鹏项目
“创新嘉兴·优才支持计划”先锋型创新团队
浙江省医学电子与数字健康重点实验室资助
