{"doi":"10.1021/jacs.4c06680","title":"HMGB3 and SUB1 Bind to and Facilitate the Repair of <i>N</i><sup>2</sup>-Alkylguanine Lesions in DNA","abstract":"N 2 -Alkyl-2′-deoxyguanosine ( N 2 -alkyl-dG) is a major type of minor-groove DNA lesions arising from endogenous metabolic processes and exogenous exposure to environmental contaminants. The N 2 -alkyl-dG lesions, if left unrepaired, can block DNA replication and transcription and induce mutations in these processes. Nevertheless, the repair pathways for N 2 -alkyl-dG lesions remain incompletely elucidated. By utilizing a photo-cross-linking coupled with mass spectrometry-based quantitative proteomic analysis, we identified a series of candidate N 2 -alkyl-dG-binding proteins. We found that two of these proteins, i.e., high-mobility group protein B3 (HMGB3) and SUB1, could bind directly to N 2 - n Bu-dG-containing duplex DNA in vitro and promote the repair of this lesion in cultured human cells. In addition, HMGB3 and SUB1 protected cells against benzo[ a ]pyrene-7,8-diol-9,10-epoxide (BPDE). SUB1 exhibits preferential binding to both the cis and trans diastereomers of N 2 -BPDE-dG over unmodified dG. On the other hand, HMGB3 binds favorably to trans - N 2 -BPDE-dG; the protein, however, does not distinguish cis - N 2 -BPDE-dG from unmodified dG. Consistently, genetic ablation of HMGB3 conferred diminished repair of trans - N 2 -BPDE-dG, but not its cis counterpart, whereas loss of SUB1 conferred attenuated repair of both diastereomers. Together, we identified proteins involved in the cellular sensing and repair of minor-groove N 2 -alkyl-dG lesions and documented a unique role of HMGB3 in the stereospecific recognition and repair of N 2 -BPDE-dG.","journal":"Journal of the American Chemical Society","year":2024,"id":445220,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":446924,"name":"Xiaomei He","orcid":"0000-0002-2077-3778","position":1,"is_corresponding":false},{"id":1261169,"name":"Xiaochen Liang","orcid":"0009-0007-3998-4536","position":2,"is_corresponding":false},{"id":404557,"name":"Andrew H. Kellum","orcid":"0000-0003-4178-8175","position":3,"is_corresponding":false},{"id":930575,"name":"Feng Tang","orcid":"0000-0001-9748-3712","position":4,"is_corresponding":false},{"id":248720,"name":"Jiekai Yin","orcid":null,"position":5,"is_corresponding":false},{"id":1261170,"name":"Su Guo","orcid":"0000-0001-9925-848X","position":6,"is_corresponding":false},{"id":704489,"name":"Yinan Wang","orcid":"0000-0001-8030-9494","position":7,"is_corresponding":false},{"id":257140,"name":"Zi Gao","orcid":null,"position":9,"is_corresponding":false},{"id":110450,"name":"Yinsheng Wang","orcid":"0000-0001-5565-283X","position":10,"is_corresponding":false},{"id":1260885,"name":"Ting Zhao","orcid":"0000-0002-9921-3692","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:42.089235Z","pmid":"39101269","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":[]}