ArticlePLoS genetics2011
AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Novel Molecular Insights and Evolution of Less Toxic Therapeutic Strategies in Burkitt Lymphoma.Cancers · 2025Review
- Rat1 promotes premature transcription termination at R-loops.Nucleic acids research · 2024Article
- Gut-derived Endotoxin-TLR4 Signaling Drives MYC-Ig Translocation to Promote Lymphoproliferation through c-JUN and STAT3 Activation.Molecular cancer research : MCR · 2023Article
- Co-expression patterns explain how a basic transcriptional role for MYC modulatesCell cycle (Georgetown, Tex.) · 2022Article
- Untangling the crosstalk between BRCA1 and R-loops during DNA repair.Nucleic acids research · 2021Review
- Review
- Splicing, genome stability and disease: splice like your genome depends on it!Current genetics · 2019Review
- R Loops and Links to Human Disease.Journal of molecular biology · 2017Review
- Cytosine deamination and base excision repair cause R-loop-induced CAG repeat fragility and instability inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Review
- Article
- The SAGA Deubiquitination Module Promotes DNA Repair and Class Switch Recombination through ATM and DNAPK-Mediated γH2AX Formation.Cell reports · 2016Article
- RNA Polymerase Collision versus DNA Structural Distortion: Twists and Turns Can Cause Break Failure.Molecular cell · 2016Review
- The spliceosome-associated protein Nrl1 suppresses homologous recombination-dependent R-loop formation in fission yeast.Nucleic acids research · 2016Article
- R loops: new modulators of genome dynamics and function.Nature reviews. Genetics · 2015Review
- QmRLFS-finder: a model, web server and stand-alone tool for prediction and analysis of R-loop forming sequences.Nucleic acids research · 2015Article
- RNA Exosome Regulates AID DNA Mutator Activity in the B Cell Genome.Advances in immunology · 2015Review
- Out of balance: R-loops in human disease.PLoS genetics · 2014Review
- Transcription and recombination: when RNA meets DNA.Cold Spring Harbor perspectives in biology · 2014Review
- Arginine methylation facilitates the recruitment of TOP3B to chromatin to prevent R loop accumulation.Molecular cell · 2014Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription of the switch (S) regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID), triggering class switch recombination (CSR), as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs) which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ). AID-induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID-mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID-mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.