{"doi":"10.3390/ijms241210168","title":"UV-DDB as a General Sensor of DNA Damage in Chromatin: Multifaceted Approaches to Assess Its Direct Role in Base Excision Repair","abstract":"<jats:p>Base excision repair (BER) is a cellular process that removes damaged bases arising from exogenous and endogenous sources including reactive oxygen species, alkylation agents, and ionizing radiation. BER is mediated by the actions of multiple proteins which work in a highly concerted manner to resolve DNA damage efficiently to prevent toxic repair intermediates. During the initiation of BER, the damaged base is removed by one of 11 mammalian DNA glycosylases, resulting in abasic sites. Many DNA glycosylases are product-inhibited by binding to the abasic site more avidly than the damaged base. Traditionally, apurinic/apyrimidinic endonuclease 1, APE1, was believed to help turn over the glycosylases to undergo multiple rounds of damaged base removal. However, in a series of papers from our laboratory, we have demonstrated that UV-damaged DNA binding protein (UV-DDB) stimulates the glycosylase activities of human 8-oxoguanine glycosylase (OGG1), MUTY DNA glycosylase (MUTYH), alkyladenine glycosylase/N-methylpurine DNA glycosylase (AAG/MPG), and single-strand selective monofunctional glycosylase (SMUG1), between three- and five-fold. Moreover, we have shown that UV-DDB can assist chromatin decompaction, facilitating access of OGG1 to 8-oxoguanine damage in telomeres. This review summarizes the biochemistry, single-molecule, and cell biology approaches that our group used to directly demonstrate the essential role of UV-DDB in BER.</jats:p>","journal":"International Journal of Molecular Sciences","year":2023,"id":35882,"datarank":0.1759083546865552,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.011116511386338745,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.011116511386338745,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":182885,"name":"Bennett Van Houten","orcid":"0000-0002-4009-2478","position":1,"is_corresponding":false},{"id":182884,"name":"Sripriya J. Raja","orcid":"0000-0001-6853-869X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37373320","pmcid":"PMC10298998","openalex_id":"https://openalex.org/W4380992534","authors":[],"funders":[{"funder_name":"NIH","grant_id":"R35ES031638","title":null},{"funder_name":"NIH","grant_id":"S10OD032158-01A1","title":null},{"funder_name":"NIH","grant_id":"1S10OD032158-01A1","title":"Lumicks C-Trap Optical Tweezers with Confocal Fluorescence Microscope"},{"funder_name":"NIH","grant_id":"2P30CA047904","title":null},{"funder_name":"National Institutes of Health","grant_id":"3P30CA047904-07S1","title":"CANCER CENTER SUPPORT GRANT"},{"funder_name":"National Institutes of Health","grant_id":"5R35ES031638-05","title":"Watching cooperative interactions between base and nucleotide excision repair proteins"}],"total_grants":6,"fwci":0.2907,"citation_percentile":0.62571838,"influential_citations":0,"citation_trend":[{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/24/12/10168/pdf?version=1686822020","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/24/12/10168/pdf?version=1686822020","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/24/12/10168/pdf?version=1686822020","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/24/12/10168/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms241210168","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37373320","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10298998","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms241210168","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10298998/pdf/ijms-24-10168.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10298998","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10298998?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/ijms241210168","host_type":""}],"fields_of_study":["DNA Repair Mechanisms","DNA and Nucleic Acid Chemistry","CRISPR and Genetic Engineering","Medicine","Biology","Chemistry","Environmental Science","Humans","Chromatin","DNA Repair","DNA Damage","DNA Glycosylases","DNA-(Apurinic or Apyrimidinic Site) Lyase","Hydrocarbons, Chlorinated"],"mesh_terms":["Chromatin","DNA Damage","DNA Repair","Humans","Hydrocarbons, Chlorinated","DNA-(Apurinic or Apyrimidinic Site) Lyase","DNA Glycosylases"],"keywords":["DNA glycosylase","AP site","DNA-(apurinic or apyrimidinic site) lyase","MUTYH","Base excision repair","AP endonuclease","DNA repair","DNA damage","DNA","Biochemistry","Biology","Chromatin","Nucleotide excision repair","Chemistry","Cell biology","Nucleosome","Single molecule","Dna Glycosylases","Uv-ddb","Hydrocarbons, Chlorinated","Humans","Review"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T10:44:47.801285Z","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":[]}