ArticleProceedings of the National Academy of Sciences of the United States of America2005
DNA cleavage in immunoglobulin somatic hypermutation depends on de novo protein synthesis but not on uracil DNA glycosylase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- RNA 2'-O-methylation promotes persistent R-loop formation and AID-mediated IgH class switch recombination.BMC biology · 2024Article
- Phf5a regulates DNA repair in class switch recombination via p400 and histone H2A variant deposition.The EMBO journal · 2021Article
- The IGH locus relocalizes to a "recombination compartment" in the perinucleolar region of differentiating B-lymphocytes.Oncotarget · 2017Article
- Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability.Nature communications · 2016Article
- Epigenetics of Peripheral B-Cell Differentiation and the Antibody Response.Frontiers in immunology · 2015Review
- APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- APOBEC3 deaminases induce hypermutation in human papillomavirus 16 DNA upon beta interferon stimulation.Journal of virology · 2014Article
- The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation.The Journal of biological chemistry · 2012Article
- Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Foxp3 expression in p53-dependent DNA damage responses.The Journal of biological chemistry · 2010Article
- Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID.The Journal of experimental medicine · 2010Article
- Article
- The C-terminal region of activation-induced cytidine deaminase is responsible for a recombination function other than DNA cleavage in class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Further evidence for involvement of a noncanonical function of uracil DNA glycosylase in class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- AID to overcome the limitations of genomic information by introducing somatic DNA alterations.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2006Review
- The dark side of activation-induced cytidine deaminase: relationship with leukemia and beyond.International journal of hematology · 2006Review
- Biased dA/dT somatic hypermutation as regulated by the heavy chain intronic iEmu enhancer and 3'Ealpha enhancers in human lymphoblastoid B cells.Molecular immunology · 2006Article
- The cytidine deaminases AID and APOBEC-1 exhibit distinct functional properties in a novel yeast selectable system.Molecular immunology · 2006Article
- Activation-induced deaminase cloning, localization, and protein extraction from young VH-mutant rabbit appendix.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells.Journal of virology · 2005Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation-induced cytidine deaminase (AID) is required for the DNA cleavage step of Ig somatic hypermutation (SHM). However, its molecular mechanism is controversial. The RNA editing hypothesis postulates that AID deaminates cytosine in an unknown mRNA to generate a new mRNA encoding SHM endonuclease. On the other hand, the DNA deamination hypothesis explains DNA cleavage by cytosine deamination in DNA, followed by uracil removal by uracil DNA glycosylase (UNG). By using the protein synthesis inhibitor cycloheximide, we showed that SHM requires de novo protein synthesis in accord with predictions by the RNA editing hypothesis. In addition, we found that cycloheximide but not Ugi (the specific inhibitor of UNG) inhibited AID-dependent DNA cleavage in the Ig gene during SHM, by using histone H2AX focus formation as a marker of DNA cleavage. The results indicate the following order of events: AID expression, protein synthesis, DNA cleavage, and SHM. The requirement of protein synthesis but not of UNG for the DNA cleavage step of SHM forces us to reconsider the DNA deamination hypothesis and strengthens the RNA editing hypothesis.
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