R Loops and Links to Human Disease.
R Loops and Links to Human Disease.
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DOI：
10.1016/j.jmb.2016.08.031
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发表时间：
2017-10-27
影响因子：
5.6
通讯作者：
Manley JL
中科院分区：
文献类型：
--
作者：
Richard P;Manley JL
异常的R环结构越来越多地被认识到是人类疾病的重要贡献者。R环，主要是共转录的，丰富的RNA/DNA杂合体，天然形成，确实可以有益于某些基因座的转录调控。然而，它们在其他地方或特定情况下不必要的持续存在可能导致DNA双链断裂，染色体重排和超突变，这些都是基因组不稳定性的来源。参与R环分解的基因突变或导致特定基因形成R环的突变会影响细胞的正常生理学。我们在这里讨论的疾病的例子与R环的链接已被描述，以及如何致病突变可能参与疾病的发展和/或进展，包括重复相关的条件，其他神经系统疾病和癌症。
Aberrant R-loop structures are increasingly being realized as an important contributor to human disease. R loops, which are mainly co-transcriptional, abundant RNA/DNA hybrids, form naturally and can indeed be beneficial for transcription regulation at certain loci. However, their unwanted persistence elsewhere or in particular situations can lead to DNA double-strand breaks, chromosome rearrangements, and hypermutation, which are all sources of genomic instability. Mutations in genes involved in R-loop resolution or mutations leading to R-loop formation at specific genes affect the normal physiology of the cell. We discuss here the examples of diseases for which a link with R loops has been described, as well as how disease-causing mutations might participate in the development and/or progression of diseases that include repeat-associated conditions, other neurological disorders, and cancers.