Skin Cancer Induction by the Antimycotic Drug Voriconazole is Caused by Impaired DNA Damage Detection Due to Chromatin Compaction [* Cross-Reference *]

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Giovannini, Sara; Weibel, Lisa; Schittek, Birgit; Sinnberg, Tobias; Schaller, Martin; Lemberg, Christina; Fehrenbacher, Birgit; Biesemeier, Antje; Nordin, Renate; Ivanova, Irina; Kurz, Bernadett; Svilenska, Teodora; Berger, Christoph; Bourquin, Jean Pierre; Kulik, Andreas; Fassihi, Hiva; Lehmann, Alan; Sarkany, Robert; Kobert, Nikita; van Toorn, Marvin; Marteijn, Jurgen A.; French, Lars E.; Rocken, Martin; Vermeulen, Wim; Kamenisch, York; Berneburg, Mark, 2026, "Skin Cancer Induction by the Antimycotic Drug Voriconazole is Caused by Impaired DNA Damage Detection Due to Chromatin Compaction [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.FRRDSK, LIST Open Repository, V1
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Description
Phototoxicity and skin cancer are severe adverse effects of the anti-fungal drug voriconazole (VOR). These adverse effects resemble those seen in xeroderma pigmentosum, caused by defective DNA nucleotide excision repair (NER), and we show that VOR decreases NER capacity. We show that VOR treatment does not perturb the expression of NER, or other DNA damage-related genes, but that VOR localizes to heterochromatin, in complexes containing histone acetyltransferase general control of amino-acid synthesis 5-like 2. Impairment of general control of amino-acid synthesis 5-like 2 binding to histone H3 reduced acetylation of H3, restricting damage-dependent chromatin unfolding, thereby reducing NER initiation. Restoration of H3 histone acetylation using histone deacetylase inhibitors, rescued VOR-induced NER repression, thus offering a preventive therapeutic option. These findings underline the importance of DNA damage-dependent chromatin remodeling as an important prerequisite of functional DNA repair. (2024-11-01)
***This entry has been automatically imported via Infodoc(ASO) CSV by LIST harvest scripts. Please refer to https://doi.org/10.1016/j.jid.2024.03.050 for the original and latest version of the dataset and data downloads*** (2026-06-24)
Subject Physics
Keyword Damage dependent chromatin remodeling, DNA repair, Predetection-NER-impairment, Skin cancer, Voriconazole
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