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Genes 2017, 8(6), 154; doi:10.3390/genes8060154

R Loops in the Regulation of Antibody Gene Diversification

Research Institute of Molecular Pathology (IMP), Campus Vienna Biocenter-1, Vienna Biocenter, Vienna 1030, Austria
Academic Editor: Frédéric Chédin
Received: 28 March 2017 / Revised: 24 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
(This article belongs to the Special Issue R-loop Biology in Eukaryotes)
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Abstract

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. View Full-Text
Keywords: class switch recombination (CSR); activation induced deaminase (AID); R loops; Q-quadruplexes (G4) class switch recombination (CSR); activation induced deaminase (AID); R loops; Q-quadruplexes (G4)
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Pavri, R. R Loops in the Regulation of Antibody Gene Diversification. Genes 2017, 8, 154.

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