{"doi":"10.1093/nar/gkaf1227","title":"Transcription–replication collisions trigger high-fidelity replication reset","abstract":"Double-stranded DNA ends arise from external agents or cellular processes like transcription-replication collisions (TRCs), threatening genome stability. Here, we performed genomic CRISPRi screens to uncover DNA end formation factors in Escherichia coli. We discovered that translation-transcription decoupling causes DNA end formation through a TRC-dependent pathway, which is lethal when DNA end processing by RecBCD is disrupted, but not when recombination is disrupted. We find that TRCs cause replisome stalling followed by \"rear-ending\" from trailing replisomes which generates free DNA ends, rather than strand breaks. Surprisingly, these DNA ends are resolved through a process we call \"replication reset\", where the stalled replicore is degraded, without triggering recombination, the DNA damage response, or mutagenesis. This hidden replicore-degradation resets the replication cycle without consequence for the genome. This discovery reveals a novel DNA safeguard mechanism for preserving genome stability when replication is disturbed and challenges the notion that TRCs necessarily cause genome instability in bacteria.","journal":"Nucleic Acids Research","year":2025,"id":527673,"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":0.9561,"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":1405562,"name":"Kobie T Welch","orcid":null,"position":1,"is_corresponding":false},{"id":999915,"name":"Laura Deus Ramirez","orcid":"0000-0001-7598-6992","position":2,"is_corresponding":false},{"id":999914,"name":"Katelin M. Hagstrom","orcid":"0000-0002-0734-2551","position":3,"is_corresponding":false},{"id":999916,"name":"Alice X Wen","orcid":"0000-0003-3572-0481","position":4,"is_corresponding":false},{"id":1405019,"name":"Jerlene Halliday","orcid":"0000-0002-4644-0314","position":5,"is_corresponding":false},{"id":568365,"name":"Susan M. Rosenberg","orcid":"0000-0003-1444-473X","position":6,"is_corresponding":false},{"id":874803,"name":"Christophe Herman","orcid":"0000-0001-8954-7907","position":7,"is_corresponding":false},{"id":985846,"name":"Matthew Cooke","orcid":"0000-0003-0964-2715","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:50:44.062153Z","pmid":"41297800","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":[]}