{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:35:13Z","timestamp":1782977713866,"version":"3.54.5"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["IB83\/3-4"],"award-info":[{"award-number":["IB83\/3-4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TFIIH is a complex essential for transcription of protein-coding genes by RNA polymerase II, DNA repair of UV-lesions and transcription of rRNA by RNA polymerase I. Mutations in TFIIH cause the cancer prone DNA-repair disorder xeroderma pigmentosum (XP) and the developmental and premature aging disorders trichothiodystrophy (TTD) and Cockayne syndrome. A total of 50% of the TTD cases are caused by TFIIH mutations. Using TFIIH mutant patient cells from TTD and XP subjects we can show that the stress-sensitivity of the proteome is reduced in TTD, but not in XP. Using three different methods to investigate the accuracy of protein synthesis by the ribosome, we demonstrate that translational fidelity of the ribosomes of TTD, but not XP cells, is decreased. The process of ribosomal synthesis and maturation is affected in TTD cells and can lead to instable ribosomes. Isolated ribosomes from TTD patients show an elevated error rate when challenged with oxidized mRNA, explaining the oxidative hypersensitivity of TTD cells. Treatment of TTD cells with N-acetyl cysteine normalized the increased translational error-rate and restored translational fidelity. Here we describe a pathomechanism that might be relevant for our understanding of impaired development and aging-associated neurodegeneration.<\/jats:p>","DOI":"10.1093\/hmg\/ddac268","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T13:37:32Z","timestamp":1667050652000},"page":"1102-1113","source":"Crossref","is-referenced-by-count":11,"title":["TFIIH mutations can impact on translational fidelity of the ribosome"],"prefix":"10.1093","volume":"32","author":[{"given":"Fatima","family":"Khalid","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Qiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallab","family":"Maity","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Lasser","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Wiese","sequence":"additional","affiliation":[{"name":"Core Unit of Mass Spectrometry and Proteomics, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Penzo","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , 40138 Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Alupei","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-3408","authenticated-orcid":false,"given":"Donata","family":"Orioli","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche , 27100 Pavia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Scharffetter-Kochanek","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5207-2861","authenticated-orcid":false,"given":"Sebastian","family":"Iben","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University Medical Center , 89081 Ulm , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"key":"2023032011061688700_","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.dnarep.2009.10.005","article-title":"Trichothiodystrophy: from basic mechanisms to clinical implications","volume":"9","author":"Stefanini","year":"2010","journal-title":"DNA Repair (Amst)"},{"key":"2023032011061688700_","article-title":"Cockayne Syndrome","volume-title":"GeneReviews(R)","author":"Laugel","year":"1993"},{"key":"2023032011061688700_","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/ncb1108-1241","article-title":"DNA damage and ageing: new-age ideas for an age-old problem","volume":"10","author":"Garinis","year":"2008","journal-title":"Nat. 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