ArticlePLoS biology2007
DNA-dependent protein kinase inhibits AID-induced antibody gene conversion.
Article in PLoS biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- How and when organisms edit their own genomes.Nature genetics · 2025Review
- SAMHD1 enhances immunoglobulin hypermutation by promoting transversion mutation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- C-terminal region of activation-induced cytidine deaminase (AID) is required for efficient class switch recombination and gene conversion.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Checkpoint kinase 2 is required for efficient immunoglobulin diversification.Cell cycle (Georgetown, Tex.) · 2014Article
- Competition between PARP-1 and Ku70 control the decision between high-fidelity and mutagenic DNA repair.DNA repair · 2011Article
- Incorporation of dUTP does not mediate mutation of A:T base pairs in Ig genes in vivo.Nucleic acids research · 2010Article
- Temporal regulation of Ig gene diversification revealed by single-cell imaging.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Genetic evidence for single-strand lesions initiating Nbs1-dependent homologous recombination in diversification of Ig v in chicken B lymphocytes.PLoS genetics · 2009Article
- Brca1 in immunoglobulin gene conversion and somatic hypermutation.DNA repair · 2008Article
- Mutagenesis dependent upon the combination of activation-induced deaminase expression and a double-strand break.Molecular immunologyArticle
- Complexes of DNA-dependent protein kinase with single-stranded oligo-(AGGG)6: identification and possible role in modulation of ribosomal RNA transcription.Doklady. Biochemistry and biophysicsArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(D)J regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(D)J hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inactivation of the Ku70 or DNA-PKcs genes in DT40 cells elevated the rate of AID-induced gene conversion as much as 5-fold. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion.
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Registered trials
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