{"doi":"10.1126/sciadv.abf1771","title":"Polθ reverse transcribes RNA and promotes RNA-templated DNA repair","abstract":"Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2'-hydroxyl groups like retroviral RTs. Last, we find that Polθ promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Polθ was selected to accommodate template ribonucleotides during DNA repair.","journal":"Science Advances","year":2021,"id":149588,"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":104,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282454,"name":"Jiemin Zhao","orcid":"0000-0002-8939-2156","position":1,"is_corresponding":false},{"id":636281,"name":"Shane McDevitt","orcid":"0000-0001-9360-2841","position":2,"is_corresponding":false},{"id":636282,"name":"Timur Rusanov","orcid":"0000-0002-4054-3611","position":3,"is_corresponding":false},{"id":636283,"name":"Trung Hoàng","orcid":"0009-0004-4068-9065","position":4,"is_corresponding":false},{"id":637382,"name":"Nikita Borisonnik","orcid":null,"position":5,"is_corresponding":false},{"id":637383,"name":"Taylor Treddinick","orcid":null,"position":6,"is_corresponding":false},{"id":392740,"name":"Felicia Wednesday Lopezcolorado","orcid":"0000-0002-2916-6042","position":7,"is_corresponding":false},{"id":636284,"name":"Tatiana Kent","orcid":"0000-0001-8237-0184","position":8,"is_corresponding":false},{"id":636285,"name":"Labiba A. Siddique","orcid":"0000-0003-3446-3946","position":9,"is_corresponding":false},{"id":636286,"name":"Joseph S. Mallon","orcid":"0000-0002-2517-9727","position":10,"is_corresponding":false},{"id":636287,"name":"Jacklyn Huhn","orcid":"0000-0001-7503-3040","position":11,"is_corresponding":false},{"id":636288,"name":"Zainab Shoda","orcid":"0000-0003-1657-5725","position":12,"is_corresponding":false},{"id":637384,"name":"Ekaterina Kashkina","orcid":null,"position":13,"is_corresponding":false},{"id":636289,"name":"Alessandra Brambati","orcid":"0000-0002-3816-425X","position":14,"is_corresponding":false},{"id":392741,"name":"Jeremy M. Stark","orcid":"0000-0002-2625-5373","position":15,"is_corresponding":false},{"id":318117,"name":"Xiaojiang S. Chen","orcid":"0000-0001-9574-0551","position":16,"is_corresponding":false},{"id":636290,"name":"Richard T. Pomerantz","orcid":"0000-0003-1194-9871","position":17,"is_corresponding":false},{"id":637381,"name":"Gurushankar Chandramouly","orcid":null,"position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:42:56.251607Z","pmid":"34117057","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":[]}