XPD/ERCC2 mutations interfere in cellular responses to oxidative stress.

dc.contributor.authorLerner, Leticia Koch
dc.contributor.authorMoreno, Natália Cestari
dc.contributor.authorRocha, Clarissa Ribeiro Reily
dc.contributor.authorMunford, Veridiana
dc.contributor.authorSantos, Valquíria Tiago dos
dc.contributor.authorSoltys, Daniela Tathiana
dc.contributor.authorGarcia, Camila Carrião Machado
dc.contributor.authorSarasin, Alain
dc.contributor.authorMenck, Carlos Frederico Martins
dc.date.accessioned2020-04-02T19:54:54Z
dc.date.available2020-04-02T19:54:54Z
dc.date.issued2019
dc.description.abstractNucleotide excision repair (NER) is a conserved, flexible mechanism responsible for the removal of bulky, helix-distorting DNA lesions, like ultraviolet damage or cisplatin adducts, but its role in the repair of lesions generated by oxidative stress is still not clear. 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 XPDmutated 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 γ-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.pt_BR
dc.identifier.citationLERNER, L. K. et al. XPD/ERCC2 mutations interfere in cellular responses to oxidative stress. Mutagenesis, v. 34, n. 4, p 341–354, jul. 2019. Disponível em: <https://academic.oup.com/mutage/article/34/4/341/5539652>. Acesso em: 10 fev. 2020.pt_BR
dc.identifier.doihttps://doi.org/10.1093/mutage/gez020pt_BR
dc.identifier.issn1464-3804
dc.identifier.urihttp://www.repositorio.ufop.br/handle/123456789/12020
dc.identifier.uri2https://academic.oup.com/mutage/article/34/4/341/5539652pt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.titleXPD/ERCC2 mutations interfere in cellular responses to oxidative stress.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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