{"doi":"10.1158/0008-5472.can-07-6695","title":"Defective Transcription/Repair Factor IIH Recruitment to Specific UV Lesions in Trichothiodystrophy Syndrome","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>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. 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Lima-Bessa","orcid":null,"position":1,"is_corresponding":false},{"id":191782,"name":"Anne Stary","orcid":null,"position":2,"is_corresponding":false},{"id":191783,"name":"Carlos F.M. Menck","orcid":null,"position":3,"is_corresponding":false},{"id":191784,"name":"Alain Sarasin","orcid":null,"position":4,"is_corresponding":false},{"id":191780,"name":"Vanessa Chiganças","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18676829","pmcid":null,"openalex_id":"https://openalex.org/W2160890617","authors":[],"funders":[],"total_grants":0,"fwci":1.2633,"citation_percentile":0.79481063,"influential_citations":0,"citation_trend":[{"year":2013,"count":2},{"year":2014,"count":1},{"year":2016,"count":1},{"year":2018,"count":1},{"year":2019,"count":2},{"year":2023,"count":1},{"year":2025,"count":2}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://hal.science/hal-03680000","host_type":"repository"},{"url":"https://aacr.figshare.com/articles/journal_contribution/Supplementary_Figure_1_from_Defective_Transcription_Repair_Factor_IIH_Recruitment_to_Specific_UV_Lesions_in_Trichothiodystrophy_Syndrome/22373958/1/files/39819195.pdf","host_type":"GREEN"},{"url":"https://hal.science/hal-03680000","host_type":"repository"},{"url":"https://aacrjournals.org/cancerres/article-pdf/68/15/6074/2594678/6074.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1158/0008-5472.can-07-6695","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18676829","host_type":"repository"},{"url":"http://producao.usp.br/handle/BDPI/28362","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","bioluminescence and chemiluminescence research","Redox biology and oxidative stress","Biology","Medicine","Cell Line","DNA Repair","Fluorescent Antibody Technique","Humans","Pyrimidine Dimers","Transcription Factor TFIIH","Trichothiodystrophy Syndromes","Ultraviolet Rays"],"mesh_terms":["Cell Line","DNA Repair","Fluorescent Antibody Technique","Humans","Pyrimidine Dimers","Ultraviolet Rays","Transcription Factor TFIIH","Trichothiodystrophy Syndromes"],"keywords":["Transcription factor II H","Xeroderma pigmentosum","Nucleotide excision repair","Biology","Pyrimidine dimer","DNA repair","Cockayne syndrome","Genetics","Photolyase","Histone","Molecular biology","DNA"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-11T05:56:26.943675Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}