Pan Xuefeng, Jiang Nan, Chen Xifang, Zhou Xiaohong, Ding Liang, Duan Fei
School of Life Science, Beijing Institute of Technology, Beijing 100081, China; School of Basic Medicine, Hebei University, Baoding 071002, China.
School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
Yi Chuan. 2014 Dec;36(12):1185-94. doi: 10.3724/SP.J.1005.2014.1185.
R-loop is a type of three-stranded nucleic acid structure that is made up of an RNA:DNA hybrid, formed due to failing separation of a nascent RNA molecule with transcripting template in transcription or by the re-annealing of RNA molecule with one of the two strands in a double stranded DNA molecule, along with the single stranded DNA, which is either the non-template strand in the transcription bubble or the RNA substituted DNA strand. Formation of R-loops can occur when transcription goes through a genomic DNA region having a tract of G bases in the non-template strand in the transcription bubble or through a type of triplet microsatellite DNA sequences that are known to be associated with certain human diseases. The negative supercoiling forces accumulated in the transcription bubble, and the misprocessing of RNA precursors, as well as the delayed utilizations and transportations of RNA molecules to cytoplasm promote R loop formation. Many studies show that cells can manage R loop formation with efficiency, and can also process the R-loops already formed in the cell, and by which, the bad effects of R-loops on DNA replication, gene mutation and homologous recombination can be regulated. In this review, we summarize the formation and the impacts of R-loops on DNA replication, mutation rates and the frequencies of homologous recombination, and also discusse the possible role of the R-loop induced DNA replication in mediating trinucleotide repeat expansions as seen with those frequently associated with human neuromuscular degenerative diseases.
R环是一种三链核酸结构，由RNA:DNA杂交体组成，它是由于新生RNA分子在转录过程中未能与转录模板分离，或者RNA分子与双链DNA分子中的两条链之一重新退火而形成的，同时还伴随着单链DNA，它可以是转录泡中的非模板链，也可以是RNA取代的DNA链。当转录通过转录泡中非模板链上有一段G碱基的基因组DNA区域，或者通过一种已知与某些人类疾病相关的三联体微卫星DNA序列时，就会发生R环的形成。转录泡中积累的负超螺旋力、RNA前体的错误加工，以及RNA分子向细胞质的延迟利用和运输都促进了R环的形成。许多研究表明，细胞能够有效地控制R环的形成，也能够处理细胞中已经形成的R环，并且通过这种方式，可以调节R环对DNA复制、基因突变和同源重组的不良影响。在这篇综述中，我们总结了R环的形成及其对DNA复制、突变率和同源重组频率的影响，还讨论了R环诱导的DNA复制在介导三核苷酸重复扩增中的可能作用，就像在那些经常与人类神经肌肉退行性疾病相关的情况中看到的那样。
