Effects of R-loops on Genome Stability / 中国生物化学与分子生物学报

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.

Mechanism of R-loop in myelodysplastic syndromes and the treatment progress / 白血病·淋巴瘤

Almost 50% myelodysplastic syndromes (MDS) patients have different splicing factor mutations, including SF3B1, SRSF2, U2AF1. Different splicing factor mutations cause the various mechanisms of slicing abnormality and eventually lead to the similar MDS phenotypes, indicating that splicing factor mutations might generate the common pathopoiesia pathway different from slicing abnormality. Recent studies have shown that SF3B1, U2AF1 and SRSF2 mutations could contribute to the accumulation of R-loop, cause DNA damage and repair abnormality, activate ATR-Chk1 pathway and finally promote apoptosis and tumorigenesis. This paper reviews the role of R-loop in the pathogenesis of MDS and the progress of related targeted drugs.