ArticleJournal of immunology (Baltimore, Md. : 1950)2006
A role for the MutL mismatch repair Mlh3 protein in immunoglobulin class switch DNA recombination and somatic hypermutation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- UNG-RPA interaction governs the choice between high-fidelity and mutagenic uracil repair.Nucleic acids research · 2026Article
- Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease.Frontiers in endocrinology · 2023Review
- Rad52 mediates class-switch DNA recombination to IgD.Nature communications · 2022Article
- The Role of DNA Repair in Immunological Diversity: From Molecular Mechanisms to Clinical Ramifications.Frontiers in immunology · 2022Review
- Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells.Nucleic acids research · 2017Article
- Identification of Candidate Predictors of Lupus Flare.Transactions of the American Clinical and Climatological Association · 2015Review
- Genome-Wide Analysis Reveals Selective Modulation of microRNAs and mRNAs by Histone Deacetylase Inhibitor in B Cells Induced to Undergo Class-Switch DNA Recombination and Plasma Cell Differentiation.Frontiers in immunology · 2015Article
- Article
- Immunoglobulin class-switch DNA recombination: induction, targeting and beyond.Nature reviews. Immunology · 2012Review
- Mismatch-mediated error prone repair at the immunoglobulin genes.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2011Review
- Endonuclease G plays a role in immunoglobulin class switch DNA recombination by introducing double-strand breaks in switch regions.Molecular immunology · 2011Article
- Estrogen receptors bind to and activate the HOXC4/HoxC4 promoter to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, immunoglobulin class switch DNA recombination, and somatic hypermutation.The Journal of biological chemistry · 2010Article
- 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination.Nature structural & molecular biology · 2010Article
- Article
- Common variable immunodeficiency: etiological and treatment issues.International archives of allergy and immunology · 2009Review
- AID- and Ung-dependent generation of staggered double-strand DNA breaks in immunoglobulin class switch DNA recombination: a post-cleavage role for AID.Molecular immunology · 2008Article
- Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Alkyladenine DNA glycosylase (Aag) in somatic hypermutation and class switch recombination.DNA repair · 2007Article
- Role for Msh5 in the regulation of Ig class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- DNA replication to aid somatic hypermutation.Advances in experimental medicine and biology · 2007Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Class switch DNA recombination (CSR) and somatic hypermutation (SHM) are central to the maturation of the Ab response. Both processes involve DNA mismatch repair (MMR). MMR proteins are recruited to dU:dG mispairs generated by activation-induced cytidine deaminase-mediated deamination of dC residues, thereby promoting S-S region synapses and introduction of mismatches (mutations). The MutL homolog Mlh3 is the last complement of the mammalian set of MMR proteins. It is highly conserved in evolution and is essential to meiosis and microsatellite stability. We used the recently generated knockout mlh3(-/-) mice to address the role of Mlh3 in CSR and SHM. We found that Mlh3 deficiency alters both CSR and SHM. mlh3(-/-) B cells switched in vitro to IgG and IgA but displayed preferential targeting of the RGYW/WRCY (R = A or G, Y = C or T, W = A or T) motif by Sgamma1 and Sgamma3 breakpoints and introduced more insertions and fewer donor/acceptor microhomologies in Smu-Sgamma1 and Smu-Sgamma3 DNA junctions, as compared with mlh3(+/+) B cells. mlh3(-/-) mice showed only a slight decrease in the frequency of mutations in the intronic DNA downstream of the rearranged J(H)4 gene. However, the residual mutations were altered in spectrum. They comprised a decreased proportion of mutations at dA/dT and showed preferential RGYW/WRCY targeting by mutations at dC/dG. Thus, the MMR Mlh3 protein plays a role in both CSR and SHM.
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Registered trials
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