R-loops are unique, three-stranded nucleic acid structures that primarily form when an RNA molecule displaces one DNA strand and anneals to the complementary DNA strand in a double-stranded DNA molecule. R-loop formation can occur during natural processes, such as transcription, in which the nascent RNA molecule remains hybridized with the template DNA strand, while the non-template DNA strand is displaced. However, R-loops can also arise due to many non-natural processes, including DNA damage, dysregulation of RNA degradation pathways, and defects in RNA processing. Despite their prevalence throughout the whole genome, R-loops are predominantly found in actively transcribed gene regions, enabling R-loops to serve seemingly controversial roles. On one hand, the pathological accumulation of R-loops contributes to genome instability, a hallmark of cancer development that plays a role in tumorigenesis, cancer progression, and therapeutic resistance. On the other hand, R-loops play critical roles in regulating essential processes, such as gene expression, chromatin organization, class-switch recombination, mitochondrial DNA replication, and DNA repair. In this review, we summarize discoveries related to the formation, suppression, and removal of R-loops and their influence on genome instability, DNA repair, and oncogenic events. We have also discussed therapeutical opportunities by targeting pathological R-loops.
R环是一种独特的三链核酸结构，主要形成于RNA分子置换双链DNA中的一条DNA链并与互补DNA链退火结合的过程。R环可在转录等自然过程中形成，此时新生RNA分子与DNA模板链保持杂交状态，而非模板DNA链被置换。然而，R环也可能由多种非自然过程引发，包括DNA损伤、RNA降解途径失调以及RNA加工缺陷。尽管R环遍布整个基因组，但其主要富集于活跃转录的基因区域，这使得R环具有看似矛盾的双重功能。一方面，R环的病理性积累会导致基因组不稳定性——这是癌症发展的标志性特征，在肿瘤发生、癌症进展和治疗抵抗中发挥重要作用。另一方面，R环在基因表达、染色质组织、类别转换重组、线粒体DNA复制和DNA修复等重要生物学过程中发挥关键调控作用。本综述系统总结了R环形成、抑制与清除机制的相关发现，及其对基因组稳定性、DNA修复和致癌事件的影响，同时探讨了靶向病理性R环的治疗策略。
肿瘤(癌症)患者之家