ArticleNucleic acids research2021
Structural and mechanistic insights into the Artemis endonuclease and strategies for its inhibition.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Nucleases and Their Inhibitors: Exploring Biological Roles, Industrial Applications, and Challenges in Heterologous Expression.Biotechnology journal · 2026Review
- Development of Water-Trapping Pyrrole-2-carboxylic Acids as Broad-Spectrum Metallo-β-lactamase Inhibitors.Journal of medicinal chemistry · 2026Article
- Caffeine inhibits nonhomologous end joining by impairing ligase IV/XRCC4 function.Nucleic acids research · 2026Article
- Multifaceted Small Molecules as Enzyme Modulators: Cases of Drug Discovery/Repurposing Illustrating Nature's Pragmatism.BioMed research international · 2026Review
- Downregulation of ZFP36L1 contributes to methotrexate resistance in osteosarcoma through enhanced NHEJ DNA repair mechanisms.Cell death & disease · 2025Article
- Artemis (DCLRE1C) Acts as a Target to Enhance Radiotherapy Response in Triple-Negative Breast Cancer.Cancers · 2025Article
- Targeting Artemis Sensitizes B Cells to Topoisomerase 2 Poisons by Disrupting DNA-PKcs-Dependent Repair.Research square · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Computational advances in the design and discovery of artemis inhibitors for radiosensitization in cancer therapy.Frontiers in chemistry · 2025Article
- Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target.Chemical science · 2024Article
- Artemis as Predictive Biomarker of Responsiveness to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer.Current oncology (Toronto, Ont.) · 2024Article
- Article
- Structure and mechanism in non-homologous end joining.DNA repair · 2023Article
- Article
- Clinical and Genetic Characterization of Patients with Artemis Deficiency in Japan.Journal of clinical immunology · 2023Article
- 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
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Artemis (SNM1C/DCLRE1C) is an endonuclease that plays a key role in development of B- and T-lymphocytes and in dsDNA break repair by non-homologous end-joining (NHEJ). Artemis is phosphorylated by DNA-PKcs and acts to open DNA hairpin intermediates generated during V(D)J and class-switch recombination. Artemis deficiency leads to congenital radiosensitive severe acquired immune deficiency (RS-SCID). Artemis belongs to a superfamily of nucleases containing metallo-β-lactamase (MBL) and β-CASP (CPSF-Artemis-SNM1-Pso2) domains. We present crystal structures of the catalytic domain of wildtype and variant forms of Artemis, including one causing RS-SCID Omenn syndrome. The catalytic domain of the Artemis has similar endonuclease activity to the phosphorylated full-length protein. Our structures help explain the predominantly endonucleolytic activity of Artemis, which contrasts with the predominantly exonuclease activity of the closely related SNM1A and SNM1B MBL fold nucleases. The structures reveal a second metal binding site in its β-CASP domain unique to Artemis, which is amenable to inhibition by compounds including ebselen. By combining our structural data with that from a recently reported Artemis structure, we were able model the interaction of Artemis with DNA substrates. The structures, including one of Artemis with the cephalosporin ceftriaxone, will help enable the rational development of selective SNM1 nuclease inhibitors.
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