{"doi":"10.1093/nar/gkad164","title":"Base excision repair of the <i>N</i>-(2-deoxy-<scp>d</scp>-<i>erythro</i>-pentofuranosyl)-urea lesion by the hNEIL1 glycosylase","abstract":"The N-(2-deoxy-d-erythro-pentofuranosyl)-urea DNA lesion forms following hydrolytic fragmentation of cis-5R,6S- and trans-5R,6R-dihydroxy-5,6-dihydrothymidine (thymine glycol, Tg) or from oxidation of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) and subsequent hydrolysis. It interconverts between α and β deoxyribose anomers. Synthetic oligodeoxynucleotides containing this adduct are efficiently incised by unedited (K242) and edited (R242) forms of the hNEIL1 glycosylase. The structure of a complex between the active site unedited mutant CΔ100 P2G hNEIL1 (K242) glycosylase and double-stranded (ds) DNA containing a urea lesion reveals a pre-cleavage intermediate, in which the Gly2 N-terminal amine forms a conjugate with the deoxyribose C1' of the lesion, with the urea moiety remaining intact. This structure supports a proposed catalytic mechanism in which Glu3-mediated protonation of O4' facilitates attack at deoxyribose C1'. The deoxyribose is in the ring-opened configuration with the O4' oxygen protonated. The electron density of Lys242 suggests the 'residue 242-in conformation' associated with catalysis. This complex likely arises because the proton transfer steps involving Glu6 and Lys242 are hindered due to Glu6-mediated H-bonding with the Gly2 and the urea lesion. Consistent with crystallographic data, biochemical analyses show that the CΔ100 P2G hNEIL1 (K242) glycosylase exhibits a residual activity against urea-containing dsDNA.","journal":"Nucleic Acids Research","year":2023,"id":357742,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":827016,"name":"Irina G. Minko","orcid":"0000-0002-0012-2265","position":1,"is_corresponding":false},{"id":315278,"name":"Pankaj Sharma","orcid":"0000-0002-7053-1574","position":2,"is_corresponding":false},{"id":404557,"name":"Andrew H. Kellum","orcid":"0000-0003-4178-8175","position":3,"is_corresponding":false},{"id":975753,"name":"Lei Li","orcid":"0000-0003-4228-2096","position":4,"is_corresponding":false},{"id":435751,"name":"Joel M. Harp","orcid":"0000-0002-9116-5606","position":5,"is_corresponding":false},{"id":315280,"name":"T.M. Iverson","orcid":"0000-0001-8816-6352","position":6,"is_corresponding":false},{"id":490390,"name":"R. Stephen Lloyd","orcid":"0000-0001-7273-372X","position":7,"is_corresponding":false},{"id":435753,"name":"Martin Egli","orcid":"0000-0003-4145-356X","position":8,"is_corresponding":false},{"id":404560,"name":"Michael P. Stone","orcid":"0000-0002-0922-0216","position":9,"is_corresponding":false},{"id":827344,"name":"Rachana Tomar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"37014002","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":[]}