{"doi":"10.1021/acs.jpcb.4c00316","title":"Direct Measurement of 8OG Syn-Anti Flips in Mutagenic 8OG·A and Long-Range Damage-Dependent Hoogsteen Breathing Dynamics Using <sup>1</sup>H CEST NMR","abstract":"Elucidating how damage impacts DNA dynamics is essential for understanding the mechanisms of damage recognition and repair. Many DNA lesions alter their propensities to form low-populated and short-lived conformational states. However, NMR methods to measure these dynamics require isotopic enrichment, which is difficult for damaged nucleotides. Here, we demonstrate the utility of the 1 H chemical exchange saturation transfer (CEST) NMR experiment in measuring the dynamics of oxidatively damaged 8-oxoguanine (8OG) in the mutagenic 8OG syn ·A anti mismatch. Using 8OG-H7 as an NMR probe of the damaged base, we directly measured 8OG syn-anti flips to form a lowly populated (pop. ∼ 5%) and short-lived (lifetime ∼50 ms) nonmutagenic 8OG anti ·A anti . These exchange parameters were in quantitative agreement with values from 13 C off-resonance R 1ρ and CEST on the labeled partner adenine. The Watson–Crick-like 8OG syn ·A anti mismatch also rescued the kinetics of Hoogsteen motions at distant A-T base pairs, which the G·A mismatch had slowed down. The results lend further support for 8OG anti ·A anti as a minor conformational state of 8OG·A, reveal that 8OG damage can impact Hoogsteen dynamics at a distance, and demonstrate the utility of 1 H CEST for measuring damage-dependent dynamics in unlabeled DNA.","journal":"The Journal of Physical Chemistry B","year":2024,"id":463227,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"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":259604,"name":"Hashim M. Al‐Hashimi","orcid":"0000-0003-0681-1747","position":1,"is_corresponding":false},{"id":705240,"name":"Stephanie Gu","orcid":"0000-0002-6337-3731","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:04:28.838123Z","pmid":"38644782","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":[]}