{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:00:42Z","timestamp":1791284442302,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2007,11,22]],"date-time":"2007-11-22T00:00:00Z","timestamp":1195689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>T<jats:sup>\u2013<\/jats:sup>B<jats:sup>\u2013<\/jats:sup>NK<jats:sup>+<\/jats:sup> severe combined immunodeficiency (SCID) is caused by a defect in V(D)J recombination. A subset of these patients has a mutation in one of the non\u2010homologous end joining (NHEJ) genes, most frequently the <jats:italic>Artemis<\/jats:italic> gene. Artemis is involved in opening of hairpin\u2010sealed coding ends. The low levels of residual D<jats:sub><jats:sc>h<\/jats:sc><\/jats:sub>\u2010J<jats:sub><jats:sc>h<\/jats:sc><\/jats:sub> junctions that could be amplified from patients\u2019 bone marrow precursor B cells showed high numbers of palindromic (P)\u2010nucleotides. In 25% of junctions, microhomology was observed in the P\u2010nucleotide regions, whereas this phenomenon was never observed in junctions amplified from bone marrow precursor B cells from healthy controls. We utilized this difference between Artemis\u2010deficient cells and normal controls to develop a V(D)J recombination assay to determine hairpin\u2010opening activity. Mutational analysis of the <jats:italic>Artemis<\/jats:italic> gene confirmed and extended the mapping of an N\u2010terminal nuclease active site, which contains several indispensable aspartate residues. C\u2010terminal deletion mutants did not show such severe defects in the V(D)J recombination assay using transient overexpression of (mutated) Artemis protein. However, a C\u2010terminal deletion mutation causes T<jats:sup>\u2013<\/jats:sup>B<jats:sup>\u2013<\/jats:sup>NK<jats:sup>+<\/jats:sup> SCID, indicating that the Artemis C terminus is essential for V(D)J recombination at the normal Artemis expression level. The V(D)J recombination assays used in this study contribute to the diagnostic strategy for T<jats:sup>\u2013<\/jats:sup>B<jats:sup>\u2013<\/jats:sup>NK<jats:sup>+ <\/jats:sup>SCID patients.<\/jats:p>","DOI":"10.1002\/eji.200737624","type":"journal-article","created":{"date-parts":[[2007,11,22]],"date-time":"2007-11-22T13:46:51Z","timestamp":1195739211000},"page":"3522-3528","source":"Crossref","is-referenced-by-count":39,"title":["Defective Artemis nuclease is characterized by coding joints with microhomology in long palindromic\u2010nucleotide stretches"],"prefix":"10.1002","volume":"37","author":[{"given":"Mirjam","family":"van der Burg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole S.","family":"Verkaik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T.","family":"den Dekker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara H.","family":"Barendregt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Pico\u2010Knijnenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilhan","family":"Tezcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques J. 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