ArticleMolecular immunology2011
Endonuclease G plays a role in immunoglobulin class switch DNA recombination by introducing double-strand breaks in switch regions.
Article in Molecular immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Discovery of an Endonuclease G-inhibitory Ku80-peptide protecting against leukemogenic rearrangements at the MLL breakpoint cluster.Nature communications · 2026Article
- Induction of postmeiotic DNA double-strand breaks by the Pnu1 endonuclease inMolecular biology of the cell · 2025Article
- Analysis of archaic human haplotypes suggests that 5hmC acts as an epigenetic guide for NCO recombination.BMC biology · 2022Article
- Rad52 mediates class-switch DNA recombination to IgD.Nature communications · 2022Article
- Structural adaptation of vertebrate endonuclease G for 5-hydroxymethylcytosine recognition and function.Nucleic acids research · 2020Article
- Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination.Nature communications · 2017Article
- Crystal structure of endonuclease G in complex with DNA reveals how it nonspecifically degrades DNA as a homodimer.Nucleic acids research · 2016Article
- Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G.Cell reports · 2016Article
- Endonuclease G initiates DNA rearrangements at the MLL breakpoint cluster upon replication stress.Oncogene · 2015Article
- Endonuclease G preferentially cleaves 5-hydroxymethylcytosine-modified DNA creating a substrate for recombination.Nucleic acids research · 2014Article
- Immunoglobulin class-switch DNA recombination: induction, targeting and beyond.Nature reviews. Immunology · 2012Review
- BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway.Nature communications · 2012Article
- Non-apoptotic functions of apoptosis-regulatory proteins.EMBO reports · 2012Review
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Immunoglobulin (Ig) class switch DNA recombination (CSR) is the crucial mechanism diversifying the biological effector functions of antibodies. Generation of double-strand DNA breaks (DSBs), particularly staggered DSBs, in switch (S) regions of the upstream and downstream CH genes involved in the specific recombination process is an absolute requirement for CSR. Staggered DSBs would be generated through deamination of dCs on opposite DNA strands by activation-induced cytidine deaminase (AID), subsequent dU deglycosylation by uracil DNA glycosylase (Ung) and abasic site nicking by apurinic/apyrimidic endonuclease. However, consistent with the findings that significant amounts of DSBs can be detected in the IgH locus in the absence of AID or Ung, we have shown in human and mouse B cells that AID generates staggered DSBs not only by cleaving intact double-strand DNA, but also by processing blunt DSB ends generated in an AID-independent fashion. How these AID-independent DSBs are generated is still unclear. It is possible that S region DNA may undergo AID-independent cleavage by structure-specific nucleases, such as endonuclease G (EndoG). EndoG is an abundant nuclease in eukaryotic cells. It cleaves single and double-strand DNA, primarily at dG/dC residues, the preferential sites of DSBs in S region DNA. We show here that EndoG can localize to the nucleus of B cells undergoing CSR and binds to S region DNA, as shown by specific chromatin immunoprecipitation assays. Using knockout EndoG(-/-) mice and EndoG(-/-) B cells, we found that EndoG deficiency resulted in a two-fold reduction in CSR in vivo and in vitro, as demonstrated by reduced cell surface IgG1, IgG2a, IgG3 and IgA, reduced secreted IgG1, reduced circle Iγ1-Cμ, Iγ3-Cμ, Iɛ-Cμ, Iα-Cμ transcripts, post-recombination Iμ-Cγ1, Iμ-Cγ3, Iμ-Cɛ and Iμ-Cα transcripts. In addition to reduced CSR, EndoG(-/-) mice showed a significantly altered spectrum of mutations in IgH J(H)-iEμ DNA. Impaired CSR in EndoG(-/-) B cells did not stem from altered B cell proliferation or apoptosis. Rather, it was associated with significantly reduced frequency of DSBs. Thus, our findings determine a role for EndoG in the generation of S region DSBs and CSR.
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