ArticleProceedings of the National Academy of Sciences of the United States of America2013
Functional redundancy between the XLF and DNA-PKcs DNA repair factors in V(D)J recombination and nonhomologous DNA end joining.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 112 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
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- Comprehensive genetic and epigenetic characterization of Lynch-like syndrome patients.International journal of cancer · 2025Article
- Utilization of natural products in diverse pathogeneses of diseases associated with single or double DNA strand damage repair.Chinese medicine · 2025Review
- Multivalent interactions of the disordered regions of XLF and XRCC4 foster robust cellular NHEJ and drive the formation of ligation-boosting condensates in vitro.Nature structural & molecular biology · 2024Article
- Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors.Nature communications · 2024Article
- DNA-PKcs suppresses illegitimate chromosome rearrangements.Nucleic acids research · 2024Article
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- 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
- DNA Repair and Immune Response: Editorial.Biomolecules · 2022Article
- The importance of DNAPKcs for blunt DNA end joining is magnified when XLF is weakened.Nature communications · 2022Article
- Primary Founder Mutations in theInternational journal of molecular sciences · 2022Article
- Role of Paralogue of XRCC4 and XLF in DNA Damage Repair and Cancer Development.Frontiers in immunology · 2022Review
- Acetyltransferases GCN5 and PCAF Are Required for B Lymphocyte Maturation in Mice.Biomolecules · 2021Article
- The RNF8 and RNF168 Ubiquitin Ligases Regulate Pro- and Anti-Resection Activities at Broken DNA Ends During Non-Homologous End Joining.DNA repair · 2021Article
- DNA End Joining: G0-ing to the Core.Biomolecules · 2021Review
- Review
- Measuring nonhomologous end-joining, homologous recombination and alternative end-joining simultaneously at an endogenous locus in any transfectable human cell.Nucleic acids research · 2021Article
- DNA Damage Response.Biomolecules · 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
7 authors at 5 institutions in 1 country.
Funding
Abstract
Classical nonhomologous end joining (C-NHEJ) is a major mammalian DNA double-strand break (DSB) repair pathway that is required for assembly of antigen receptor variable region gene segments by V(D)J recombination. Recombination activating gene endonuclease initiates V(D)J recombination by generating DSBs between two V(D)J coding gene segments and flanking recombination signal sequences (RS), with the two coding ends and two RS ends joined by C-NHEJ to form coding joins and signal joins, respectively. During C-NHEJ, recombination activating gene factor generates two coding ends as covalently sealed hairpins and RS ends as blunt 5'-phosphorylated DSBs. Opening and processing of coding end hairpins before joining by C-NHEJ requires the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). However, C-NHEJ of RS ends, which do not require processing, occurs relatively normally in the absence of DNA-PKcs. The XRCC4-like factor (XLF) is a C-NHEJ component that is not required for C-NHEJ of chromosomal signal joins or coding joins because of functional redundancy with ataxia telangiectasia mutated kinase, a protein that also has some functional overlap with DNA-PKcs in this process. Here, we show that XLF has dramatic functional redundancy with DNA-PKcs in the V(D)J SJ joining process, which is nearly abrogated in their combined absence. Moreover, we show that XLF functionally overlaps with DNA-PKcs in normal mouse development, promotion of genomic stability in mouse fibroblasts, and in IgH class switch recombination in mature B cells. Our findings suggest that DNA-PKcs has fundamental roles in C-NHEJ processes beyond end processing that have been masked by functional overlaps with XLF.
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