Pavri Rushad
Research Institute of Molecular Pathology (IMP), Campus Vienna Biocenter-1, Vienna Biocenter, Vienna 1030, Austria.
Genes (Basel). 2017 Jun 2;8(6):154. doi: 10.3390/genes8060154.
For nearly three decades, R loops have been closely linked with class switch recombination (CSR), the process that generates antibody isotypes and that occurs via a complex cascade initiated by transcription-coupled mutagenesis in switch recombination sequences. R loops form during transcription of switch recombination sequences in vitro and in vivo, and there is solid evidence that R loops are required for efficient class switching. The classical model of R loops posits that they boost mutation rates by generating stable and long tracts of single-stranded DNA that serve as the substrate for activation induced deaminase (AID), the enzyme that initiates the CSR reaction cascade by co-transcriptionally mutating ssDNA in switch recombination sequences. Though logical and compelling, this model has not been supported by in vivo evidence. Indeed, several reports suggest that R loops may not be involved in recruiting AID activity to switch regions, meaning that R loops probably serve other unanticipated roles in CSR. Here, I review the key findings in this field to date and propose hypotheses that could help towards elucidating the precise function of R loops in CSR.
近三十年来，R环一直与类别转换重组（CSR）密切相关，CSR是产生抗体亚型的过程，通过在转换重组序列中由转录偶联诱变引发的复杂级联反应发生。R环在体外和体内的转换重组序列转录过程中形成，并且有确凿证据表明R环是高效类别转换所必需的。R环的经典模型认为，它们通过产生稳定且长的单链DNA片段来提高突变率，这些单链DNA片段作为激活诱导脱氨酶（AID）的底物，AID是一种通过共转录突变转换重组序列中的单链DNA来启动CSR反应级联的酶。尽管这个模型合乎逻辑且令人信服，但尚未得到体内证据的支持。事实上，一些报告表明，R环可能不参与将AID活性募集到转换区域，这意味着R环可能在CSR中发挥其他未预料到的作用。在此，我回顾了该领域迄今为止的关键发现，并提出了有助于阐明R环在CSR中精确功能的假设。
