ArticleThe Journal of experimental medicine2005
B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil.
Article in The Journal of experimental medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 114 citations in OpenAlex.
- Unique chicken B cell development: species-specific mechanisms and contradictory requirements of B cell receptor for post-hatched B cell development.Frontiers in immunology · 2026Review
- What is in a name? Rethinking SMUG1 in genome maintenance.NAR cancer · 2025Review
- Uracil-DNA Glycosylase fromInternational journal of molecular sciences · 2025Article
- CDADC1 is a vertebrate-specific dCTP deaminase that metabolizes gemcitabine and decitabine to prevent cellular toxicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis.Chembiochem : a European journal of chemical biology · 2025Review
- Structural and Functional Insights into UDGs.Protein and peptide letters · 2025Review
- Functional roles and cancer variants of the bifunctional glycosylase NEIL2.Environmental and molecular mutagenesis · 2024Review
- RPA guides UNG to uracil in ssDNA to facilitate antibody class switching and repair of mutagenic uracil at the replication fork.Nucleic acids research · 2024Article
- Replication Protein A Enhances Kinetics of Uracil DNA Glycosylase on ssDNA and Across DNA Junctions: Explored with a DNA Repair Complex Produced with SpyCatcher/SpyTag Ligation.Chembiochem : a European journal of chemical biology · 2023Article
- Signal-on/signal-off bead-based assays for the multiplexed monitoring of base excision repair activities by flow cytometry.Analytical and bioanalytical chemistry · 2022Article
- The Role of DNA Repair in Immunological Diversity: From Molecular Mechanisms to Clinical Ramifications.Frontiers in immunology · 2022Review
- Review
- Active DNA demethylation-The epigenetic gatekeeper of development, immunity, and cancer.Advanced genetics (Hoboken, N.J.) · 2021Review
- Intrinsic Strand-Incision Activity of Human UNG: Implications for Nick Generation in Immunoglobulin Gene Diversification.Frontiers in immunology · 2021Article
- Update on Infections in Primary Antibody Deficiencies.Frontiers in immunology · 2021Review
- HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines.Journal of translational medicine · 2020Article
- Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences.Frontiers in immunology · 2020Review
- Primary B-cell immunodeficiencies.Human immunology · 2019Review
- Mutating for Good: DNA Damage Responses During Somatic Hypermutation.Frontiers in immunology · 2019Review
- N-terminal domain of human uracil DNA glycosylase (hUNG2) promotes targeting to uracil sites adjacent to ssDNA-dsDNA junctions.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The generation of high-affinity antibodies requires somatic hypermutation (SHM) and class switch recombination (CSR) at the immunoglobulin (Ig) locus. Both processes are triggered by activation-induced cytidine deaminase (AID) and require UNG-encoded uracil-DNA glycosylase. AID has been suggested to function as an mRNA editing deaminase or as a single-strand DNA deaminase. In the latter model, SHM may result from replicative incorporation of dAMP opposite U or from error-prone repair of U, whereas CSR may be triggered by strand breaks at abasic sites. Here, we demonstrate that extracts of UNG-proficient human B cell lines efficiently remove U from single-stranded DNA. In B cell lines from hyper-IgM patients carrying UNG mutations, the single-strand-specific uracil-DNA glycosylase, SMUG1, cannot complement this function. Moreover, the UNG mutations lead to increased accumulation of genomic uracil. One mutation results in an F251S substitution in the UNG catalytic domain. Although this UNG form was fully active and stable when expressed in Escherichia coli, it was mistargeted to mitochondria and degraded in mammalian cells. Our results may explain why SMUG1 cannot compensate the UNG2 deficiency in human B cells, and are fully consistent with the DNA deamination model that requires active nuclear UNG2. Based on our findings and recent information in the literature, we present an integrated model for the initiating steps in CSR.
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