ArticlePLoS genetics2019
DSB structure impacts DNA recombination leading to class switching and chromosomal translocations in human B cells.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026Review
- Enhanced cleavage of genomicRNA biology · 2025Article
- Modular cytosine base editing promotes epigenomic and genomic modifications.Nucleic acids research · 2024Article
- TREX2 enables efficient genome disruption mediated by paired CRISPR-Cas9 nickases that generate 3'-overhanging ends.Molecular therapy. Nucleic acids · 2023Article
- TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells.Nucleic acids research · 2023Article
- Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023Review
- Altered DNA repair pathway engagement by engineered CRISPR-Cas9 nucleases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- PlmCas12e (CasX2) cleavage of CCR5: impact of guide RNA spacer length and PAM sequence on cleavage activity.RNA biology · 2023Article
- Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination.eLife · 2022Article
- Switch Tandem Repeats Influence the Choice of the Alternative End-Joining Pathway in Immunoglobulin Class Switch Recombination.Frontiers in immunology · 2022Article
- The Role of RNA in DNA Breaks, Repair and Chromosomal Rearrangements.Biomolecules · 2021Review
- Toward precise CRISPR DNA fragment editing and predictable 3D genome engineering.Journal of molecular cell biology · 2021Review
- Article
- A Tale of Loops and Tails: The Role of Intrinsically Disordered Protein Regions in R-Loop Recognition and Phase Separation.Frontiers in molecular biosciences · 2021Article
- Canonical non-homologous end-joining promotes genome mutagenesis and translocations induced by transcription-associated DNA topoisomerase 2 activity.Nucleic acids research · 2020Article
- Resection and repair of a Cas9 double-strand break at CTG trinucleotide repeats induces local and extensive chromosomal deletions.PLoS genetics · 2020Article
- The balancing act of R-loop biology: The good, the bad, and the ugly.The Journal of biological chemistry · 2020Review
- DNA Double Strand Breaks and Chromosomal Translocations Induced by DNA Topoisomerase II.Frontiers in molecular biosciences · 2019Review
- Cas9 has no exonuclease activity resulting in staggered cleavage with overhangs and predictable di- and tri-nucleotide CRISPR insertions without template donor.Cell discovery · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Class switch recombination (CSR) requires activation-induced cytidine deaminase (AID) to trigger DNA double strand breaks (DSBs) at the immunoglobulin heavy chain (IGH) in B cells. Joining of AID-dependent DSBs within IGH facilitate CSR and effective humoral immunity, but ligation to DSBs in non-IGH chromosomes leads to chromosomal translocations. Thus, the mechanism by which AID-dependent DSBs are repaired requires careful examination. The random activity of AID in IGH leads to a spectrum of DSB structures. In this report, we investigated how DSB structure impacts end-joining leading to CSR and chromosomal translocations in human B cells, for which models of CSR are inefficient and not readily available. Using CRISPR/Cas9 to model AID-dependent DSBs in IGH and non-IGH genes, we found that DSBs with 5' and 3' overhangs led to increased processing during end-joining compared to blunt DSBs. We observed that 5' overhangs were removed and 3' overhangs were filled in at recombination junctions, suggesting that different subsets of enzymes are required for repair based on DSB polarity. Surprisingly, while Cas9-mediated switching preferentially utilized NHEJ regardless of DSB structure, A-EJ strongly preferred repairing blunt DSBs leading to translocations in the absence of NHEJ. We found that DSB polarity influenced frequency of Cas9-mediated switching and translocations more than overhang length. Lastly, recombination junctions from staggered DSBs exhibited templated insertions, suggesting iterative resection and filling in during repair. Our results demonstrate that DSB structure biases repair towards NHEJ or A-EJ to complete recombination leading to CSR and translocations, thus helping to elucidate the mechanism of genome rearrangements in human B cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.