ArticleNucleic acids research2022
Physical ARTEMIS:DNA-PKcs interaction is necessary for V(D)J recombination.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis.Nature communications · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Against all odds: The road to success in the development of human immune reconstitution mice.Animal models and experimental medicine · 2024Review
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- The cGAS-Ku80 complex regulates the balance between two end joining subpathways.Cell death and differentiation · 2024Article
- DNA-PK controls Apollo's access to leading-end telomeres.Nucleic acids research · 2024Article
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- Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility.Nucleic acids research · 2023Article
- DNA Repair Deficiency Regulates Immunity Response in Cancers: Molecular Mechanism and Approaches for Combining Immunotherapy.Cancers · 2023Review
- Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Article
- Structure and Function of SNM1 Family Nucleases.Advances in experimental medicine and biology · 2023Review
- Dynamics of the Artemis and DNA-PKcs Complex in the Repair of Double-Strand Breaks.Journal of molecular biology · 2022Review
- Partial deletions of the autoregulatory C-terminal domain of Artemis and their effect on its nuclease activity.DNA repair · 2022Article
- Structural analysis of the basal state of the Artemis:DNA-PKcs complex.Nucleic acids research · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclease ARTEMIS and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are involved in the repair of physiological and pathogenic DNA double strand breaks. Both proteins are indispensable for the hairpin-opening activity in V(D)J recombination and therefore essential for the adaptive immune response. ARTEMIS and DNA-PKcs interact, however experimental evidence for in vivo significance is missing. We demonstrate that mutations abolishing this protein-protein interaction affect nuclease function. In DNA-PKcs, mutation L3062R impairs the physical interaction with ARTEMIS and was previously identified as pathogenic variant, resulting in radiosensitive severe combined immunodeficiency. In ARTEMIS, specific mutations in two conserved regions affect interaction with DNA-PKcs. In combination they impair V(D)J recombination activity, independent of ARTEMIS autoinhibitory self-interaction between the ARTEMIS C-terminus and the N-terminal nuclease domain. We describe small fragments from both proteins, capable of interaction with the corresponding full-length partner proteins: In DNA-PKcs 42 amino acids out of FAT region 2 (PKcs3041-3082) can mediate interaction with ARTEMIS. In the nuclease we have defined 26 amino acids (ARM378-403) as minimal DNA-PKcs interacting fragment. The exact mapping of the ARTEMIS:DNA-PKcs interaction may pave the way for the design of specific inhibitors targeting the repair of DNA double strand breaks.
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