dc.contributor.author | van der Burg, Mirjam | |
dc.contributor.author | IJspeert, Hanna | |
dc.contributor.author | Verkaik, Nicole S. | |
dc.contributor.author | Turul, Tuba | |
dc.contributor.author | Wiegant, Wouter W. | |
dc.contributor.author | Morotomi-Yano, Keiko | |
dc.contributor.author | Mari, Pierre-Olivier | |
dc.contributor.author | Tezcan, Ilhan | |
dc.contributor.author | Chen, David J. | |
dc.contributor.author | Zdzienicka, Malgorzata Z. | |
dc.contributor.author | van Dongen, Jacques J. M. | |
dc.contributor.author | van Gent, Dik C. | |
dc.date.accessioned | 2019-12-10T10:42:07Z | |
dc.date.available | 2019-12-10T10:42:07Z | |
dc.date.issued | 2009 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | https://doi.org/10.1172/JCI37141 | |
dc.identifier.uri | http://hdl.handle.net/11655/14217 | |
dc.description.abstract | Radiosensitive T-B- severe combined immunodeficiency (RS-SCID) is caused by defects in the nonhomologous end-joining (NHEJ) DNA repair pathway, which results in failure of functional V(D)J recombination. Here we have identified the first human RS-SCID patient to our knowledge with a DNA-PKcs missense mutation (L3062R). The causative mutation did not affect the kinase activity or DNA end-binding capacity of DNA-PKcs itself; rather, the presence of long P-nucleotide stretches in the immunoglobulin coding joints indicated that it caused insufficient Artemis activation, something that is dependent on Artemis interaction with autophosphorylated DNA-PKcs. Moreover, overall end-joining activity was hampered, suggesting that Artemis-independent DNA-PKcs functions were also inhibited. This study demonstrates that the presence of DNA-PKcs kinase activity is not sufficient to rule out a defect in this gene during diagnosis and treatment of RS-SCID patients. Further, the data suggest that residual DNA-PKcs activity is indispensable in humans. | |
dc.language.iso | en | |
dc.publisher | Amer Soc Clinical Investigation Inc | |
dc.relation.isversionof | 10.1172/JCI37141 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Research & Experimental Medicine | |
dc.title | A Dna-Pkcs Mutation in A Radiosensitive T-B- Scid Patient Inhibits Artemis Activation And Nonhomologous End-Joining | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.relation.journal | Journal Of Clinical Investigation | |
dc.contributor.department | Çocuk Sağlığı ve Hastalıkları | |
dc.identifier.volume | 119 | |
dc.identifier.issue | 1 | |
dc.identifier.startpage | 91 | |
dc.identifier.endpage | 98 | |
dc.description.index | WoS | |
dc.description.index | Scopus | |