ArticleDNA repair2022
The mRNA tether model for activation-induced deaminase and its relevance for Ig somatic hypermutation and class switch recombination.
Article in DNA repair, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- AID self-assembly and multistranded DNA binding drive synapsis in class switch recombination.Nucleic acids research · 2026Article
- A dynamic RNA hub facilitates activation-induced cytidine deaminase recruitment to the immunoglobulin heavy-chain locus.Molecular cell · 2026Article
- A dynamic RNA hub facilitates activation induced cytidine deaminase recruitment to the immunoglobulin heavy chain locus.bioRxiv : the preprint server for biology · 2026Article
- Review
- Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities.Nature communications · 2024Article
- The RNA tether model for human chromosomal translocation fragile zones.Trends in biochemical sciences · 2024Review
- Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination.eLife · 2022Article
- AID function in somatic hypermutation and class switch recombination.Acta biochimica et biophysica Sinica · 2022Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Activation-induced deaminase (AID) only deaminates cytosine within single-stranded DNA. Transcription is known to increase AID deamination on duplex DNA substrates during transcription. Using a purified T7 RNA polymerase transcription system, we recently found that AID deamination of a duplex DNA substrate is reduced if RNase A is added during transcription. This finding prompted us to consider that the mRNA tail may contribute to AID action at the nearby transcribed strand (TS) or non-transcribed strand (NTS) of DNA, which are transiently single-stranded in the wake of RNA polymerase movement. Here, we used a purified system to test whether a single-stranded oligonucleotide (oligo) consisting of RNA in the 5' portion and DNA in the 3' portion (i.e., 5'RNA-DNA3', also termed an RNA-DNA fusion substrate) could be deaminated equally efficiently as the same sequence when it is entirely DNA. We found that AID acts on the RNA-DNA fusion substrate and the DNA-only substrate with similar efficiency. Based on this finding and our recent observation on the importance of the mRNA tail, we propose a model in which the proximity and length of the mRNA tail provide a critical site for AID loading to permit a high local collision frequency with the NTS and TS in the transient wake of the RNA polymerase. When the mRNA tail is not present, we know that AID action drops to levels equivalent to when there is no transcription at all. This mRNA tether model explains several local and global features of Ig somatic hypermutation and Ig class switch recombination, while integrating structural and functional features of AID.
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