{"doi":"10.1093/nar/gkaf304","title":"A non-tethering role for the <i>Drosophila</i> Pol θ linker domain in promoting damage resolution","abstract":"DNA polymerase theta (Pol θ) is an error-prone translesion polymerase that becomes crucial for DNA double-strand break repair when cells are deficient in homologous recombination or non-homologous end joining. In some organisms, Pol θ also promotes tolerance of DNA interstrand crosslinks. Due to its importance in DNA damage tolerance, Pol θ is an emerging target for treatment of cancer and disease. Prior work has characterized the functions of the Pol θ helicase-like and polymerase domains, but the roles of the linker domain are largely unknown. Here, we show that the Drosophila melanogaster Pol θ linker domain promotes proper egg development and is required for repair of DNA double-strand breaks and interstrand crosslink tolerance. While a linker domain with scrambled amino acid residues is sufficient for DNA repair, replacement of the linker with part of the Homo sapiens Pol θ linker or a disordered region from the FUS RNA-binding protein does not restore function. These results demonstrate that the linker domain is not simply a random tether between the catalytic domains and suggest that intrinsic amino acid residue properties, rather than protein interaction motifs, are more critical for Pol θ linker functions in DNA repair.","journal":"Nucleic Acids Research","year":2025,"id":539314,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"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":895865,"name":"Nicholas B. Woodward","orcid":"0000-0002-4205-1864","position":1,"is_corresponding":false},{"id":1003614,"name":"Manan Krishnamurthy","orcid":"0000-0001-8906-0533","position":2,"is_corresponding":false},{"id":305530,"name":"Mitch McVey","orcid":"0000-0001-8883-0188","position":3,"is_corresponding":false},{"id":1003613,"name":"Justin R. Blanch","orcid":"0000-0002-9939-7700","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:52:30.048313Z","pmid":"40275613","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":[]}