{"doi":"10.1101/2025.09.17.676973","title":"Eukaryotic Lagging Strand Synthesis is Distributive","abstract":"SUMMARY DNA’s anti-parallel structure presents a topological challenge to the replisome, as the leading and lagging strands must be synthesized in opposite directions. It is widely believed that the lagging strand polymerases Pol δ and Pol α are stably tethered to the eukaryotic replisome to facilitate their recycling and to coordinate leading and lagging strand synthesis. To test this idea, we directly visualized the dynamics of Pol α/δ at active replication forks via single-molecule imaging in Xenopus nuclear extracts. Surprisingly, we find that neither Pol α nor Pol δ is stably tethered to the eukaryotic replisome. Instead, lagging strand synthesis occurs distributively and entails the recruitment of new molecules of Pol α and Pol δ to facilitate the synthesis of new Okazaki fragments. Our data reveal a highly dynamic mechanism of lagging strand synthesis and challenge the current textbook model of the eukaryotic replisome.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559084,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":551660,"name":"Gheorghe Chistol","orcid":"0000-0003-4868-3667","position":1,"is_corresponding":false},{"id":227873,"name":"Luke D. Lynch","orcid":"0000-0002-1948-2316","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","pmid":"41000965","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":[]}