ArticleProceedings of the National Academy of Sciences of the United States of America2021
Ku70 suppresses alternative end joining in G1-arrested progenitor B cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 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
- 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination.Science advances · 2026Article
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining at double-ended DSBs.Nucleic acids research · 2026Article
- Review
- ATM and 53BP1 regulate alternative end joining-mediated V(D)J recombination.Science advances · 2024Article
- Noodles, the all-in-one system for on-target efficiency analysis of CRISPR guide RNAs.MethodsX · 2024Article
- DNA-PKcs suppresses illegitimate chromosome rearrangements.Nucleic acids research · 2024Article
- Current Strategies for Increasing Knock-In Efficiency in CRISPR/Cas9-Based Approaches.International journal of molecular sciences · 2024Review
- Higher Expression of Ku80 and Ku70 Indicates Hotter Tumor Immune Microenvironment in Hepatocellular Carcinoma and Better CTL-Centered Immunotherapy.Journal of inflammation research · 2024Article
- Shifted PAMs generate DNA overhangs and enhance SpCas9 post-catalytic complex dissociation.Nature structural & molecular biology · 2023Article
- FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2023Article
- 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
- FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.bioRxiv : the preprint server for biology · 2023Article
- The splicing regulators TIA1 and TIAL1 are required for the expression of the DNA damage repair machinery during B cell lymphopoiesis.Cell reports · 2022Article
- Article
- 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
- DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022Review
- V(D)J Recombination: Recent Insights in Formation of the Recombinase Complex and Recruitment of DNA Repair Machinery.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Classical nonhomologous end joining (C-NHEJ) repairs DNA double-strand breaks (DSBs) throughout interphase but predominates in G1 phase when homologous recombination is unavailable. Complexes containing the Ku70/80 ("Ku") and XRCC4/ligase IV (Lig4) core C-NHEJ factors are required, respectively, for sensing and joining DSBs. While XRCC4/Lig4 are absolutely required for joining RAG1/2 endonuclease ("RAG")-initiated DSBs during V(D)J recombination in G1-phase progenitor lymphocytes, cycling cells deficient for XRCC4/Lig4 also can join chromosomal DSBs by alternative end-joining (A-EJ) pathways. Restriction of V(D)J recombination by XRCC4/Lig4-mediated joining has been attributed to RAG shepherding V(D)J DSBs exclusively into the C-NHEJ pathway. Here, we report that A-EJ of DSB ends generated by RAG1/2, Cas9:gRNA, and Zinc finger endonucleases in Lig4-deficient G1-arrested progenitor B cell lines is suppressed by Ku. Thus, while diverse DSBs remain largely as free broken ends in Lig4-deficient G1-arrested progenitor B cells, deletion of Ku70 increases DSB rejoining and translocation levels to those observed in Ku70-deficient counterparts. Correspondingly, while RAG-initiated V(D)J DSB joining is abrogated in Lig4-deficient G1-arrested progenitor B cell lines, joining of RAG-generated DSBs in Ku70-deficient and Ku70/Lig4 double-deficient lines occurs through a translocation-like A-EJ mechanism. Thus, in G1-arrested, Lig4-deficient progenitor B cells are functionally end-joining suppressed due to Ku-dependent blockage of A-EJ, potentially in association with G1-phase down-regulation of Lig1. Finally, we suggest that differential impacts of Ku deficiency versus Lig4 deficiency on V(D)J recombination, neuronal apoptosis, and embryonic development results from Ku-mediated inhibition of A-EJ in the G1 cell cycle phase in Lig4-deficient developing lymphocyte and neuronal cells.
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