ArticleProceedings of the National Academy of Sciences of the United States of America2020
CtIP-mediated DNA resection is dispensable for IgH class switch recombination by alternative end-joining.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Ku70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of the Ku ring along DNA.Nucleic acids research · 2026Article
- Visualization and quantification of rDNA instabilities in mammalian cells and mouse models.Nucleic acids research · 2026Article
- Polymerase theta repairs persistent G1-induced DNA breaks in S-phase during class switch recombination.Nature communications · 2025Article
- Article
- Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.Nature communications · 2023Article
- Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice.Nucleic acids research · 2022Article
- SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination.Nature communications · 2022Article
- Alternative end-joining in BCR gene rearrangements and translocations.Acta biochimica et biophysica Sinica · 2022Review
- Switch Tandem Repeats Influence the Choice of the Alternative End-Joining Pathway in Immunoglobulin Class Switch Recombination.Frontiers in immunology · 2022Article
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
- DNA damage-induced phosphorylation of CtIP at a conserved ATM/ATR site T855 promotes lymphomagenesis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- FATC Domain Deletion Compromises ATM Protein Stability, Blocks Lymphocyte Development, and Promotes Lymphomagenesis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Cancer-Associated ATM R3008H Mutation Reveals the Link between ATM Activation and Its Exchange.Cancer research · 2021Article
- Multiple DSB Resection Activities Redundantly Promote Alternative End Joining-Mediated Class Switch Recombination.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
To generate antibodies with different effector functions, B cells undergo Immunoglobulin Heavy Chain (IgH) class switch recombination (CSR). The ligation step of CSR is usually mediated by the classical nonhomologous end-joining (cNHEJ) pathway. In cNHEJ-deficient cells, a remarkable ∼25% of CSR can be achieved by the alternative end-joining (Alt-EJ) pathway that preferentially uses microhomology (MH) at the junctions. While A-EJ-mediated repair of endonuclease-generated breaks requires DNA end resection, we show that CtIP-mediated DNA end resection is dispensable for A-EJ-mediated CSR using cNHEJ-deficient B cells. High-throughput sequencing analyses revealed that loss of ATM/ATR phosphorylation of CtIP at T855 or ATM kinase inhibition suppresses resection without altering the MH pattern of the A-EJ-mediated switch junctions. Moreover, we found that ATM kinase promotes Alt-EJ-mediated CSR by suppressing interchromosomal translocations independent of end resection. Finally, temporal analyses reveal that MHs are enriched in early internal deletions even in cNHEJ-proficient B cells. Thus, we propose that repetitive IgH switch regions represent favored substrates for MH-mediated end-joining contributing to the robustness and resection independence of A-EJ-mediated CSR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.