{"doi":"10.3390/ijms22052698","title":"Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways","abstract":"<jats:p>The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.</jats:p>","journal":"International Journal of Molecular Sciences","year":2021,"id":36019,"datarank":0.617670219850219,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.2114626896848874,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.2114626896848874,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":14,"citers_with_citation_signal":11,"citers_with_endowment":11,"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":183244,"name":"Nicholas E. Geacintov","orcid":null,"position":1,"is_corresponding":false},{"id":183243,"name":"Vladimir Shafirovich","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.70805020110221,"endowment":2.70805020110221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33800059","pmcid":"PMC7962115","openalex_id":"https://openalex.org/W3133687763","authors":[],"funders":[{"funder_name":"National Institute of Environmental Health Sciences","grant_id":"R01 ES-027059","title":null},{"funder_name":"National Institute of Environmental Health Sciences","grant_id":"R21 ES-028546","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"R01 ES027059","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"R21 ES028546","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01ES027059-03","title":"Interplay between DNA repair mechanisms in human cells and extracts"},{"funder_name":"National Institutes of Health","grant_id":"5R21ES028546-02","title":"Determining DNA Repair Capacities for Correlations with DNA Adductomes"}],"total_grants":6,"fwci":0.8141,"citation_percentile":0.70286895,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":2},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/22/5/2698/pdf?version=1615117369","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/22/5/2698/pdf?version=1615117369","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/22/5/2698/pdf?version=1615117369","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/22/5/2698/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms22052698","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33800059","host_type":"repository"},{"url":"https://doaj.org/article/f368f96e58524b619e6c78945c91d0e2","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms22052698","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7962115","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7962115","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7962115?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/ijms22052698","host_type":""}],"fields_of_study":["DNA Repair Mechanisms","DNA and Nucleic Acid Chemistry","Carcinogens and Genotoxicity Assessment","Medicine","Biology","Chemistry","0301 basic medicine","0303 health sciences","03 medical and health sciences","DNA Repair","Free Radicals","Genetic Vectors","Guanine","Humans","Oxidation-Reduction","Plasmids"],"mesh_terms":["DNA Repair","Free Radicals","Genetic Vectors","Guanine","Humans","Oxidation-Reduction","Plasmids"],"keywords":["Guanine","Nucleotide excision repair","DNA","Base excision repair","DNA damage","DNA repair","Plasmid","DNA glycosylase","Biology","Molecular biology","Base pair","Chemistry","Cell biology","Biochemistry","Nucleotide","Gene","Reactive oxygen species","Oxidative stress","Guanine Oxidation","Free Radicals","Genetic Vectors","Humans","Review","Oxidation-Reduction","Plasmids"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T13:27:47.657494Z","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":[]}