{"doi":"10.1093/nar/gkad281","title":"<i>Saccharomyces cerevisiae</i> DNA polymerase IV overcomes Rad51 inhibition of DNA polymerase δ in Rad52-mediated direct-repeat recombination","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Saccharomyces cerevisiae DNA polymerase IV (Pol4) like its homolog, human DNA polymerase lambda (Polλ), is involved in Non-Homologous End-Joining and Microhomology-Mediated Repair. Using genetic analysis, we identified an additional role of Pol4 also in homology-directed DNA repair, specifically in Rad52-dependent/Rad51-independent direct-repeat recombination. Our results reveal that the requirement for Pol4 in repeat recombination was suppressed by the absence of Rad51, suggesting that Pol4 counteracts the Rad51 inhibition of Rad52-mediated repeat recombination events. Using purified proteins and model substrates, we reconstituted in vitro reactions emulating DNA synthesis during direct-repeat recombination and show that Rad51 directly inhibits Polδ DNA synthesis. Interestingly, although Pol4 was not capable of performing extensive DNA synthesis by itself, it aided Polδ in overcoming the DNA synthesis inhibition by Rad51. In addition, Pol4 dependency and stimulation of Polδ DNA synthesis in the presence of Rad51 occurred in reactions containing Rad52 and RPA where DNA strand-annealing was necessary. Mechanistically, yeast Pol4 displaces Rad51 from ssDNA independent of DNA synthesis. Together our in vitro and in vivo data suggest that Rad51 suppresses Rad52-dependent/Rad51-independent direct-repeat recombination by binding to the primer-template and that Rad51 removal by Pol4 is critical for strand-annealing dependent DNA synthesis.</jats:p>","journal":"Nucleic Acids Research","year":2023,"id":31450,"datarank":0.5023227196169563,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.14263842869720061,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.14263842869720061,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":9,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":168552,"name":"Damon Meyer","orcid":null,"position":1,"is_corresponding":false},{"id":168553,"name":"Lilin Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":168554,"name":"Benjamin Mallory","orcid":null,"position":3,"is_corresponding":false},{"id":88224,"name":"Jie Liu","orcid":"0000-0003-1398-5411","position":4,"is_corresponding":false},{"id":168555,"name":"Becky Xu Hua Fu","orcid":null,"position":5,"is_corresponding":false},{"id":168556,"name":"Xiaoping Zhang","orcid":null,"position":6,"is_corresponding":false},{"id":168557,"name":"Wolf-Dietrich Heyer","orcid":"0000-0002-7774-1953","position":7,"is_corresponding":false},{"id":168551,"name":"Paula G Cerqueira","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37070185","pmcid":"PMC10287921","openalex_id":"https://openalex.org/W4366238403","authors":[],"funders":[{"funder_name":"NIH","grant_id":"GM32431","title":null},{"funder_name":"Science without Borders Program of Brazil","grant_id":"CA108459","title":null},{"funder_name":"National Institutes of Health","grant_id":"GM58015","title":null},{"funder_name":"National Institutes of Health","grant_id":"GM137751","title":null},{"funder_name":"Cancer Center Core Support Grant NCI","grant_id":"P30CA093373","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM137751","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM118129","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA108459","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM058015","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM032431","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM058015-12","title":"Recombinational mechanisms of DNA repair in eukaryotes"},{"funder_name":"National Institutes of Health","grant_id":"5R01GM137751-03","title":"Genome instability induced by homologous recombination"},{"funder_name":"National Institutes of Health","grant_id":"3P30CA093373-07S2","title":"Cancer Center Support Grant - P30"},{"funder_name":"University of California","grant_id":"","title":null}],"total_grants":14,"fwci":1.4537,"citation_percentile":0.81575196,"influential_citations":0,"citation_trend":[{"year":2023,"count":3},{"year":2024,"count":4},{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad281/50004586/gkad281.pdf","host_type":"journal"},{"url":"https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad281/50004586/gkad281.pdf","host_type":"GOLD"},{"url":"https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkad281/50004586/gkad281.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/nar/article-pdf/51/11/5547/50669518/gkad281.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/nar/gkad281","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37070185","host_type":"repository"},{"url":"https://escholarship.org/uc/item/2z0735rb","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10287921","host_type":"repository"},{"url":"https://escholarship.org/content/qt2z0735rb/qt2z0735rb.pdf","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10287921/pdf/gkad281.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10287921","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10287921?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1093/nar/gkad281","host_type":""},{"url":"https://doi.org/https://doi.org/10.1093/nar/gkad281","host_type":""}],"fields_of_study":["DNA Repair Mechanisms","Carcinogens and Genotoxicity Assessment","Genetic Neurodegenerative Diseases","Medicine","Biology","Humans","DNA","DNA Polymerase beta","DNA Polymerase III","DNA Repair","Rad51 Recombinase","Rad52 DNA Repair and Recombination Protein","Recombinational DNA Repair","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins"],"mesh_terms":["DNA","DNA Polymerase III","DNA Repair","Humans","Saccharomyces cerevisiae","DNA Polymerase beta","Saccharomyces cerevisiae Proteins","Rad51 Recombinase","Rad52 DNA Repair and Recombination Protein","Recombinational DNA Repair"],"keywords":["RAD51","Biology","RAD52","DNA polymerase","DNA polymerase II","Homologous recombination","DNA clamp","In vitro recombination","DNA polymerase delta","Molecular biology","FLP-FRT recombination","DNA repair","Polymerase","Replication protein A","DNA","Processivity","DNA polymerase mu","Saccharomyces cerevisiae","Primer (cosmetics)","Genetics","Genetic recombination","Circular bacterial chromosome","DNA-binding protein","Yeast","Recombination","Reverse transcriptase","Chemistry","Molecular cloning","Gene","Complementary DNA","Polymerase chain reaction","Transcription factor","570","Saccharomyces cerevisiae Proteins","Recombinational DNA Repair","Biological Sciences","Genome Integrity, Repair and Replication","540","Rad52 DNA Repair and Recombination Protein","Environmental sciences","Chemical sciences","Information and Computing Sciences","Humans","Biochemistry and Cell Biology","Generic health relevance","Rad51 Recombinase","DNA Polymerase beta","Biotechnology","Developmental Biology","DNA Polymerase III"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T07:11:45.644605Z","pmid":null,"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":[]}