ArticleMolecular immunology2020
DNA-PKcs chemical inhibition versus genetic mutation: Impact on the junctional repair steps of V(D)J recombination.
Article in Molecular immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Targeting Artemis sensitizes acute lymphoblastic leukemia cells to topoisomerase 2 poisons by disrupting DNA-PKcs-dependent repair.Communications biology · 2026Article
- Targeting Artemis Sensitizes B Cells to Topoisomerase 2 Poisons by Disrupting DNA-PKcs-Dependent Repair.Research square · 2025Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- DNA-PKcs suppresses illegitimate chromosome rearrangements.Nucleic acids research · 2024Article
- DNA-PK and ATM drive phosphorylation signatures that antagonistically regulate cytokine responses to herpesvirus infection or DNA damage.Cell systems · 2024Article
- DNA-PKcs regulates myogenesis in an Akt-dependent manner independent of induced DNA damage.Cell death and differentiation · 2023Article
- The DNA binding domain and the C-terminal region of DNA Ligase IV specify its role in V(D)J recombination.PloS one · 2023Article
- Structure and Function of SNM1 Family Nucleases.Advances in experimental medicine and biology · 2023Review
- Structural analysis of the basal state of the Artemis:DNA-PKcs complex.Nucleic acids research · 2022Article
- Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand.Molecules (Basel, Switzerland) · 2021Article
- Temporally uncoupled signal and coding joint formation in human V(D)J recombination.Molecular immunology · 2020Article
- The molecular basis and disease relevance of non-homologous DNA end joining.Nature reviews. Molecular cell biology · 2020Review
- Structural analysis of the catalytic domain of Artemis endonuclease/SNM1C reveals distinct structural features.The Journal of biological chemistry · 2020Article
- Review
- The flexible and iterative steps within the NHEJ pathway.Progress in biophysics and molecular biologyArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Spontaneous DNA-PKcs deficiencies in animals result in a severe combined immunodeficiency (SCID) phenotype because DNA-PKcs is required to activate Artemis for V(D)J recombination coding end hairpin opening. The impact on signal joint formation in these spontaneous mutant mammals is variable. Genetically engineered DNA-PKcs null mice and cells from them show a >1,000-fold reduction in coding joint formation and minimal reduction in signal joint formation during V(D)J recombination. Does chemical inhibition of DNA-PKcs mimic this phenotype? M3814 (also known as Nedisertib) is a potent DNA-PKcs inhibitor. We find here that M3814 causes a quantitative reduction in coding joint formation relative to signal joint formation. The sequences of signal and coding junctions were within normal limits, though rare coding joints showed novel features. The signal junctions generally did not show evidence of resection into the signal ends that is often seen in cells that have genetic defects in DNA-PKcs. Comparison of the chemical inhibition findings here with the known results for spontaneous and engineered DNA-PKcs mutant mammals is informative for considering pharmacologic small molecule inhibition of DNA-PKcs in various types of neoplasia.
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Registered trials
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.