ArticleMolecular immunology2008
AID- and Ung-dependent generation of staggered double-strand DNA breaks in immunoglobulin class switch DNA recombination: a post-cleavage role for AID.
Article in Molecular immunology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- B cell TET2 recruits OGT for nuclear TET2 and H2B O-GlcNAcylation to drive AID and BLIMP-1 expression and maturation of the antibody response.Cell reports · 2026Article
- Investigating population-level immunosenescence: From bench to bedside.Frontiers in immunology · 2022Review
- Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination.Nature communications · 2017Article
- Engineering and optimising deaminase fusions for genome editing.Nature communications · 2016Article
- DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID.Cell reports · 2015Article
- Elucidation of IgH 3' region regulatory role during class switch recombination via germline deletion.Nature communications · 2015Article
- Elucidation of the enigmatic IgD class-switch recombination via germline deletion of the IgH 3' regulatory region.The Journal of experimental medicine · 2014Article
- Attenuating homologous recombination stimulates an AID-induced antileukemic effect.The Journal of experimental medicine · 2013Article
- Rev1 recruits ung to switch regions and enhances du glycosylation for immunoglobulin class switch DNA recombination.Cell reports · 2012Article
- Altered pattern of immunoglobulin hypermutation in mice deficient in Slip-GC protein.The Journal of biological chemistry · 2012Article
- Immunoglobulin class-switch DNA recombination: induction, targeting and beyond.Nature reviews. Immunology · 2012Review
- Iron inhibits activation-induced cytidine deaminase enzymatic activity and modulates immunoglobulin class switch DNA recombination.The Journal of biological chemistry · 2012Article
- Article
- 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
- HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation.Nature immunology · 2009Article
- Article
- Regulation of aicda expression and AID activity: relevance to somatic hypermutation and class switch DNA recombination.Critical reviews in immunology · 2007Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Class switch DNA recombination (CSR) substitutes an immunoglobulin (Ig) constant heavy chain (C(H)) region with a different C(H) region, thereby endowing an antibody with different biological effector functions. CSR requires activation-induced cytidine deaminase (AID) and occurrence of double-strand DNA breaks (DSBs) in S regions of upstream and downstream C(H) region genes. DSBs are critical for CSR and would be generated through deamination of dC by AID, subsequent dU deglycosylation by uracil DNA glycosylase (Ung) and nicking by apurinic/apyrimidic endonuclease (APE) of nearby abasic sites on opposite DNA strands. We show here that in human and mouse B cells, S region DSBs can be generated in an AID- and Ung-independent fashion. These DSBs are blunt and 5'-phosphorylated. In B cells undergoing CSR, blunt and 5'-phosphorylated DSBs are processed in an AID- and Ung-dependent fashion to yield staggered DNA ends. Blunt and 5'-phosphorylated DSBs can be readily detected in human and mouse AID- or Ung-deficient B cells. These B cells are CSR defective, but show evidence of intra-S region recombination. Forced expression of AID in AID-negative B cells converts blunt S region DSBs to staggered DSBs. Conversely, forced expression of dominant negative AID or inhibition of Ung by Ung inhibitor (Ugi) in switching B cells abrogates the emergence of staggered DSBs and concomitant CSR. Thus, AID and Ung generate staggered DSBs not only by cleaving intact double-strand DNA, but also by processing blunt DSB ends, whose generation is AID- and Ung-independent, thereby outlining a post-cleavage role for AID in CSR.
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Registered trials
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