Defective Transcription/Repair Factor IIH Recruitment to Specific UV Lesions in Trichothiodystrophy Syndrome
| Autor: | Keronninn M. Lima-Bessa, Carlos Frederico Martins Menck, Alain Sarasin, Vanessa Chiganças, Anne Stary |
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| Přispěvatelé: | Institut Gustave Roussy (IGR), Universidade de São Paulo (USP) |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Xeroderma pigmentosum DNA Repair Ultraviolet Rays DNA repair DNA damage Trichothiodystrophy Fluorescent Antibody Technique [SDV.CAN]Life Sciences [q-bio]/Cancer Pyrimidine dimer Biology Cell Line medicine Humans Trichothiodystrophy Syndromes MESH: Trichothiodystrophy Syndromes [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Photolyase MESH: Fluorescent Antibody Technique MESH: DNA Repair MESH: Humans MESH: Pyrimidine Dimers MESH: Transcription Factor TFIIH medicine.disease Molecular biology MESH: Cell Line [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Oncology Pyrimidine Dimers Transcription factor II H MESH: Ultraviolet Rays Transcription Factor TFIIH Nucleotide excision repair |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2008, 68 (15), pp.6074-6083. ⟨10.1158/0008-5472.CAN-07-6695⟩ |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-07-6695 |
| Popis: | Most trichothiodystrophy (TTD) patients present mutations in the xeroderma pigmentosum D (XPD) gene, coding for a subunit of the transcription/repair factor IIH (TFIIH) complex involved in nucleotide excision repair (NER) and transcription. After UV irradiation, most TTD/XPD patients are more severely affected in the NER of cyclobutane pyrimidine dimers (CPD) than of 6-4-photoproducts (6-4PP). The reasons for this differential DNA repair defect are unknown. Here we report the first study of NER in response to CPDs or 6-4PPs separately analyzed in primary fibroblasts. This was done by using heterologous photorepair; recombinant adenovirus vectors carrying photolyases enzymes that repair CPD or 6-4PP specifically by using the energy of light were introduced in different cell lines. The data presented here reveal that some TTD/XPD mutations affect the recruitment of TFIIH specifically to CPDs, but not to 6-4PPs. This deficiency is further confirmed by the inability of TTD/XPD cells to recruit, specifically for CPDs, NER factors that arrive in a TFIIH-dependent manner later in the NER pathway. For 6-4PPs, we show that TFIIH complexes carrying an NH2-terminal XPD mutated protein are also deficient in recruitment of NER proteins downstream of TFIIH. Treatment with the histone deacetylase inhibitor trichostatin A allows the recovery of TFIIH recruitment to CPDs in the studied TTD cells and, for COOH-terminal XPD mutations, increases the repair synthesis and survival after UV, suggesting that this defect can be partially related with accessibility of DNA damage in closed chromatin regions. [Cancer Res 2008;68(15):6074–83] |
| Databáze: | OpenAIRE |
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