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The helicase XPD\/ERCC2, one of the two helicases of the transcription complex IIH, together with XPB, participates both in NER and in RNA pol II-driven transcription. In this work, we investigated the responses of distinct XPD-mutated cell lines to the oxidative stress generated by photoactivated methylene blue (MB) and KBrO3 treatments. The studied cells are derived from patients with XPD mutations but expressing different clinical phenotypes, including xeroderma pigmentosum (XP), XP and Cockayne syndrome (XP-D\/CS) and trichothiodystrophy (TTD). We show by different approaches that all XPD-mutated cell lines tested were sensitive to oxidative stress, with those from TTD patients being the most sensitive. Host cell reactivation (HCR) assays showed that XP-D\/CS and TTD cells have severely impaired repair capacity of oxidised lesions in plasmid DNA, and alkaline comet assays demonstrated the induction of significantly higher amounts of DNA strand breaks after treatment with photoactivated MB in these cells compared to wild-type cells. All XPD-mutated cells presented strong S\/G2 arrest and persistent \u03b3-H2AX staining after photoactivated MB treatment. Taken together, these results indicate that XPD participates in the repair of lesions induced by the redox process, and that XPD mutations lead to differences in the response to oxidatively induced damage.<\/jats:p>","DOI":"10.1093\/mutage\/gez020","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T07:15:39Z","timestamp":1562742939000},"page":"341-354","source":"Crossref","is-referenced-by-count":19,"title":["<i>XPD\/ERCC2<\/i>\n                    mutations interfere in cellular responses to oxidative stress"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3476-5231","authenticated-orcid":false,"given":"Leticia K","family":"Lerner","sequence":"first","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia C","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa R R","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veridiana","family":"Munford","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valqu\u00edria","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela T","family":"Soltys","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila C M","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Federal University of Ouro Preto , Ouro Preto, MG,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Sarasin","sequence":"additional","affiliation":[{"name":"CNRS-UMR8200, Institut Gustave Roussy, Universit\u00e9 Paris-Sud , Villejuif,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F M","family":"Menck","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo, SP,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"2026041420120595500_CIT0001","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2008.04.030","article-title":"XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations","volume":"133","author":"Fan","year":"2008","journal-title":"Cell"},{"key":"2026041420120595500_CIT0002","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.cell.2008.04.029","article-title":"Structure of the DNA repair helicase XPD","volume":"133","author":"Liu","year":"2008","journal-title":"Cell"},{"key":"2026041420120595500_CIT0003","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1371\/journal.pbio.0060149","article-title":"Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD","volume":"6","author":"Wolski","year":"2008","journal-title":"PLoS Biol."},{"key":"2026041420120595500_CIT0004","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nature23903","article-title":"The cryo-electron microscopy structure of human transcription factor IIH","volume":"549","author":"Greber","year":"2017","journal-title":"Nature"},{"key":"2026041420120595500_CIT0005","doi-asserted-by":"crossref","first-page":"a012609","DOI":"10.1101\/cshperspect.a012609","article-title":"Nucleotide excision repair in eukaryotes","volume":"5","author":"Sch\u00e4rer","year":"2013","journal-title":"Cold Spring Harb. 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