Effects of R-loops on Genome Stability
10.13865/j.cnki.cjbmb.2022.11.1421
- Author:
Tu-Nan XU
1
;
Yan-Jun GUO
2
;
Wei-Wei PAN
2
Author Information
1. College of Pharmaceutical Science, Zhejiang University of Technology
2. Department of Cell Biology, College of Medicine, Jiaxing University
- Publication Type:Journal Article
- Keywords:
genomic stability;
R-loop;
RNA: DNA hybrid;
senataxin
- From:
Chinese Journal of Biochemistry and Molecular Biology
2023;39(9):1238-1246
- CountryChina
- Language:Chinese
-
Abstract:
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 (topo) 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 carried 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 diseases, and explores the possibility of using R-loops as a therapeutic target in the future.
