{"doi":"10.1016/j.celrep.2025.116136","title":"Structural basis for dual DNA and RNA specificity of the G-quadruplex-resolving DEAH-box helicase DHX36","abstract":"DEAH-box helicases, which share a structurally conserved ATPase core, function in all facets of eukaryotic gene expression. While most helicases are highly specialized for their substrates, DHX36 (DEAH-box helicase 36) resolves both DNA and RNA G-quadruplexes. To elucidate the molecular basis of this versatility, we have determined cryo-electron microscopy structures of bovine DHX36 bound to a three-tier RNA G-quadruplex and a six-tier DNA G-quadruplex at 2.6 and 3.4 Å resolution, respectively. Kinetic and smFRET characterizations of structure-guided mutants indicate a key role for the RecA2 domain of the helicase core in DNA vs. RNA discrimination. Furthermore, our structures show that a sequence-divergent RecA2 domain surface loop synergizes with a DHX36-specific N-terminal extension to orthogonally recognize features that specify G-quadruplexes over other nucleic acid structures. Our analysis suggests that recognizing their folded substrates by DEAH-box helicases may generally involve ornamentations of their structural cores acting synergistically with specialized peripheral elements.","journal":"Cell Reports","year":2025,"id":524212,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":475672,"name":"Tapas Paul","orcid":"0000-0001-7508-5676","position":1,"is_corresponding":false},{"id":251550,"name":"Jiansen Jiang","orcid":"0000-0002-1692-7906","position":2,"is_corresponding":false},{"id":284455,"name":"Sua Myong","orcid":"0000-0001-9098-3423","position":3,"is_corresponding":false},{"id":321054,"name":"A.R. Ferré-D′Amaré","orcid":"0000-0003-4549-1619","position":4,"is_corresponding":false},{"id":633881,"name":"Michael T. Banco","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:50:12.083054Z","pmid":"40833853","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":[]}