{"doi":"10.1073/pnas.2024258118","title":"DDX11 loss causes replication stress and pharmacologically exploitable DNA repair defects","abstract":"Significance Replication stress can affect development and is a hallmark of cancers. Warsaw breakage syndrome is a developmental disorder caused by mutations in the conserved DDX11 DNA helicase. Here, using human cellular models of DDX11 deficiency, we report that DDX11 helicase prevents replication stress and mediates homology-directed repair via homologous recombination. Mechanistically, DDX11 promotes resection, enabling RPA and RAD51 focus formation, and acts nonredundantly with the RAD51 mediators BRCA1 and BRCA2. As a result, targeting DDX11 confers improved chemotherapy responsiveness in both chemotherapy-sensitive and drug-resistant BRCA1/2-mutated cancers that regained homologous recombination proficiency by suppressor mutation or somatic reversion. The results pinpoint DDX11 as a critical replication stress mitigating factor whose targeting can improve chemotherapeutic response in a range of cancers.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":160294,"datarank":1.013275092649186,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.47163740575255236,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.47163740575255236,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":34,"citers_with_citation_signal":26,"citers_with_endowment":26,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"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":590313,"name":"Dana Branzei","orcid":"0000-0002-0544-4888","position":1,"is_corresponding":false},{"id":672771,"name":"Nanda Kumar Jegadesan","orcid":"0000-0002-2710-0656","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:43.908634Z","pmid":"33879618","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":[]}