{"doi":"10.1101/2022.10.07.511343","title":"UV irradiation remodels the specificity landscape of transcription factors","abstract":"ABSTRACT Somatic mutations are highly enriched at transcription factor (TF) binding sites, with the strongest trend being observed for ultraviolet light (UV)-induced mutations in melanomas. One of the main mechanisms proposed for this hyper-mutation pattern is the inefficient repair of UV lesions within TF-binding sites, caused by competition between TFs bound to these lesions and the DNA repair proteins that must recognize the lesions to initiate repair. However, TF binding to UV-irradiated DNA is poorly characterized, and it is unclear whether TFs maintain specificity for their DNA sites after UV exposure. We developed UV-Bind, a high-throughput approach to investigate the impact of UV irradiation on protein-DNA binding specificity. We applied UV-Bind to ten TFs from eight structural families, and found that UV lesions significantly altered the DNA-binding preferences of all TFs tested. The main effect was a decrease in binding specificity, but the precise effects and their magnitude differ across factors. Importantly, we found that despite the overall reduction in DNA-binding specificity in the presence of UV lesions, TFs can still compete with repair proteins for lesion recognition, in a manner consistent with their specificity for UV-irradiated DNA. In addition, for a subset of TFs we identified a surprising but reproducible effect at certain non-consensus DNA sequences, where UV irradiation leads to a high increase in the level of TF binding. These changes in DNA-binding specificity after UV irradiation, at both consensus and non-consensus sites, have important implications for the regulatory and mutagenic roles of TFs in the cell.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":312248,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":4627,"name":"Yuning Zhang","orcid":"0000-0002-2967-4207","position":1,"is_corresponding":false},{"id":1009682,"name":"Yiling Liu","orcid":"0000-0002-6872-0106","position":2,"is_corresponding":false},{"id":506060,"name":"Matthew A. Schaich","orcid":"0000-0001-6771-5623","position":3,"is_corresponding":false},{"id":676201,"name":"Brittani L Schnable","orcid":null,"position":4,"is_corresponding":false},{"id":1009683,"name":"Debbie Burdinski","orcid":"0000-0002-5625-3619","position":5,"is_corresponding":false},{"id":251360,"name":"Sheera Adar","orcid":"0000-0002-9767-3740","position":6,"is_corresponding":false},{"id":259601,"name":"Miles A. Pufall","orcid":"0000-0002-7022-6916","position":7,"is_corresponding":false},{"id":182885,"name":"Bennett Van Houten","orcid":"0000-0002-4009-2478","position":8,"is_corresponding":false},{"id":4639,"name":"Raluca Gordân","orcid":"0000-0002-6404-6556","position":9,"is_corresponding":false},{"id":4630,"name":"Ariel Afek","orcid":"0000-0001-8584-9879","position":10,"is_corresponding":false},{"id":259600,"name":"Zachery Mielko","orcid":"0000-0002-1935-9203","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:33:36.072096Z","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":[]}