Giovannini, Sara and Weibel, Lisa and Schittek, Birgit and Sinnberg, Tobias and Schaller, Martin and Lemberg, Christina and Fehrenbacher, Birgit and Biesemeier, Antje and Nordin, Renate and Ivanova, Irina and Kurz, Bernadett and Svilenska, Teodora and Berger, Christoph and Bourquin, Jean-Pierre and Kulik, Andreas and Fassihi, Hiva and Lehmann, Alan and Sarkany, Robert and Kobert, Nikita and van Toorn, Marvin and Marteijn, Jurgen A. and French, Lars E. and Rocken, Martin and Vermeulen, Wim and Kamenisch, York and Berneburg, Mark (2024) Skin Cancer Induction by the Antimycotic Drug Voriconazole Is Caused by Impaired DNA Damage Detection Due to Chromatin Compaction. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 144 (11). pp. 2465-2476. ISSN 0022-202X, 1523-1747
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NUCLEOTIDE EXCISION-REPAIR; SQUAMOUS-CELL CARCINOMA; TRANSPLANT RECIPIENTS; ACETYLATION; PHOTOSENSITIVITY; PHOTOTOXICITY; THERAPY; PHOTOCARCINOGENESIS; MELANOSOMES; Damage dependent chromatin remodeling; DNA repair; Predetection-NER-impairment; Skin cancer; Voriconazole |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jan 2026 10:54 |
| Last Modified: | 22 Jan 2026 10:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65042 |
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