{"doi":"10.1093/nar/gkac1201","title":"Structural basis of DNA polymerase θ mediated DNA end joining","abstract":"DNA polymerase θ (Pol θ) plays an essential role in the microhomology-mediated end joining (MMEJ) pathway for repairing DNA double-strand breaks. However, the mechanisms by which Pol θ recognizes microhomologous DNA ends and performs low-fidelity DNA synthesis remain unclear. Here, we present cryo-electron microscope structures of the polymerase domain of Lates calcarifer Pol θ with long and short duplex DNA at up to 2.4 Å resolution. Interestingly, Pol θ binds to long and short DNA substrates similarly, with extensive interactions around the active site. Moreover, Pol θ shares a similar active site as high-fidelity A-family polymerases with its finger domain well-closed but differs in having hydrophilic residues surrounding the nascent base pair. Computational simulations and mutagenesis studies suggest that the unique insertion loops of Pol θ help to stabilize short DNA binding and assemble the active site for MMEJ repair. Taken together, our results illustrate the structural basis of Pol θ-mediated MMEJ.","journal":"Nucleic Acids Research","year":2022,"id":258227,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":623526,"name":"Hanwen Zhu","orcid":"0000-0002-6172-0189","position":1,"is_corresponding":false},{"id":850083,"name":"Shikai Jin","orcid":"0000-0001-9525-4166","position":2,"is_corresponding":false},{"id":909835,"name":"Leora Maksoud","orcid":null,"position":3,"is_corresponding":false},{"id":465026,"name":"Nikhil Jain","orcid":"0000-0002-9091-6156","position":4,"is_corresponding":false},{"id":7161,"name":"Ji Sun","orcid":"0000-0002-9302-3177","position":5,"is_corresponding":false},{"id":678959,"name":"Yang Gao","orcid":"0000-0002-4037-0431","position":6,"is_corresponding":false},{"id":909314,"name":"Chuxuan Li","orcid":"0000-0001-9386-9909","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T00:25:38.634785Z","pmid":"36583344","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":[]}