ArticleProceedings of the National Academy of Sciences of the United States of America2011
Decrease in topoisomerase I is responsible for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- BRIP1, a G-quadruplex DNA helicase, protects against AID-induced genomic instability by limiting R-loop accumulation.Molecular medicine (Cambridge, Mass.) · 2026Article
- 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
- The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026Review
- Ago2 and a miRNA reduce Topoisomerase 1 for enhancing DNA cleavage in antibody diversification by activation-induced cytidine deaminase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Topoisomerases in Immune Cell Development and Function.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- The IgHFrontiers in immunology · 2023Article
- CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes.Nature communications · 2021Article
- Immunometabolism and potential targets in severe COVID-19 peripheral immune responses.Asian journal of pharmaceutical sciences · 2021Article
- Native Co-immunoprecipitation Assay to Identify Interacting Partners of Chromatin-associated Proteins in Mammalian Cells.Bio-protocol · 2020Article
- SAMHD1-mediated dNTP degradation is required for efficient DNA repair during antibody class switch recombination.The EMBO journal · 2020Article
- RNA-binding motifs of hnRNP K are critical for induction of antibody diversification by activation-induced cytidine deaminase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Functional Consequences of Eukaryotic Topoisomerase 1 Interaction with G-Quadruplex DNA.Genes · 2020Review
- The Interplay between G-quadruplex and Transcription.Current medicinal chemistry · 2019Review
- AIMP3 Deletion Induces Acute Radiation Syndrome-like Phenotype in Mice.Scientific reports · 2018Article
- Epigenomic Modifications Mediating Antibody Maturation.Frontiers in immunology · 2018Review
- The Top1 paradox: Friend and foe of the eukaryotic genome.DNA repair · 2017Review
- Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability.Nature communications · 2016Article
- Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy.Biomolecules · 2015Review
- Topoisomerase I deficiency causes RNA polymerase II accumulation and increases AID abundance in immunoglobulin variable genes.DNA repair · 2015Article
- Identification of DNA cleavage- and recombination-specific hnRNP cofactors for activation-induced cytidine deaminase.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Somatic hypermutation (SHM) and class-switch recombination (CSR) of the Ig gene require both the transcription of the locus and the expression of activation-induced cytidine deaminase (AID). During CSR, AID decreases the amount of topoisomerase I (Top1); this decrease alters the DNA structure and induces cleavage in the S region. Similarly, Top1 is involved in transcription-associated mutation at dinucleotide repeats in yeast and in triplet-repeat contraction in mammals. Here, we report that the AID-induced decrease in Top1 is critical for SHM. Top1 knockdown or haploinsufficiency enhanced SHM, whereas Top1 overexpression down-regulated it. A specific Top1 inhibitor, camptothecin, suppressed SHM, indicating that Top1's activity is required for DNA cleavage. Nonetheless, suppression of transcription abolished SHM, even in cells with Top1 knockdown, suggesting that transcription is critical. These results are consistent with a model proposed for CSR and triplet instability, in which transcription-induced non-B structure formation is enhanced by Top1 reduction and provides the target for irreversible cleavage by Top1. We speculate that the mechanism for transcription-coupled genome instability was adopted to generate immune diversity when AID evolved.
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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.