ArticleProceedings of the National Academy of Sciences of the United States of America2026
R-loop disruption triggers irreversible topoisomerase 1-DNA cleavage complex formation during AID-dependent IgH gene diversification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- R-loop disruption triggers irreversible topoisomerase 1-DNA cleavage complex formation during AID-dependent IgH gene diversification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Class switch recombination (CSR) and somatic hypermutation are essential mechanisms of effective antibody production, dependent on the enzyme activation-induced cytidine deaminase (AID). Since AID lacks the intrinsic ability to cleave DNA, topoisomerase 1 (TOP1) has been hypothesized to mediate AID- and transcription-dependent DNA cleavage. However, the molecular mechanism underlying the formation of an irreversible TOP1-DNA cleavage complex (TOP1-CC) following cytidine to uridine (C-to-U) editing by AID remains undefined. To unveil this mechanism, we tested antisense oligonucleotides (ASOs) targeting noncoding germline transcripts (GLTs) that form R-loops across DNA cleavage sites during CSR. These studies revealed that the anti-GLT-ASOs increased DNA cleavage frequency, concomitant with a decrease in R-loops. Mechanistically, ASO-mediated R-loop disruption led to increased TOP1-CC formation specifically within the GLT region during CSR. Furthermore, an in vitro transcription assay demonstrated that RNase H-mediated R-loop degradation enhanced positive supercoiling and double-strand breaks in the presence of TOP1, even in the absence of AID. Moreover, knockout of Tyrosyl-DNA phosphodiesterase 1 (
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.