{"doi":"10.1126/science.ado3867","title":"Structure and repair of replication-coupled DNA breaks","abstract":"Using CRISPR-Cas9 nicking enzymes, we examined the interaction between the replication machinery and single-strand breaks, one of the most common forms of endogenous DNA damage. We show that replication fork collapse at leading-strand nicks generates resected single-ended double-strand breaks (seDSBs) that are repaired by homologous recombination (HR). If these seDSBs are not promptly repaired, arrival of adjacent forks creates double-ended DSBs (deDSBs), which could drive genomic scarring in HR-deficient cancers. deDSBs can also be generated directly when the replication fork bypasses lagging-strand nicks. Unlike deDSBs produced independently of replication, end resection at nick-induced seDSBs and deDSBs is BRCA1-independent. Nevertheless, BRCA1 antagonizes 53BP1 suppression of RAD51 filament formation. These results highlight distinctive mechanisms that maintain replication fork stability.","journal":"Science","year":2024,"id":416831,"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":97,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9612,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":248584,"name":"Veenu Tripathi","orcid":null,"position":1,"is_corresponding":false},{"id":557102,"name":"Kyle B. Vrtis","orcid":"0000-0002-9851-0396","position":2,"is_corresponding":false},{"id":458971,"name":"Dali Zong","orcid":"0000-0001-6019-2970","position":3,"is_corresponding":false},{"id":260578,"name":"Raj Chari","orcid":"0000-0002-2216-313X","position":4,"is_corresponding":false},{"id":246622,"name":"Elsa Callén","orcid":"0000-0002-6325-0221","position":5,"is_corresponding":false},{"id":1160357,"name":"Ajith V. Pankajam","orcid":"0000-0002-4457-9523","position":6,"is_corresponding":false},{"id":92410,"name":"Gang Zhen","orcid":null,"position":7,"is_corresponding":false},{"id":848617,"name":"Gabriel Matos‐Rodrigues","orcid":"0000-0003-4085-7810","position":8,"is_corresponding":false},{"id":1202037,"name":"Jiajie Yang","orcid":null,"position":9,"is_corresponding":false},{"id":558485,"name":"Shuheng Wu","orcid":null,"position":10,"is_corresponding":false},{"id":824081,"name":"Giordano Reginato","orcid":"0009-0002-5284-4339","position":11,"is_corresponding":false},{"id":246623,"name":"Wei Wu","orcid":"0000-0001-5164-2765","position":12,"is_corresponding":false},{"id":316515,"name":"Petr Ćejka","orcid":"0000-0002-9087-032X","position":13,"is_corresponding":false},{"id":251359,"name":"Johannes C. Walter","orcid":"0000-0002-4186-7570","position":14,"is_corresponding":false},{"id":248586,"name":"André Nussenzweig","orcid":null,"position":15,"is_corresponding":false},{"id":621611,"name":"Raphael Pavani","orcid":"0000-0002-7187-2995","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T01:56:44.873714Z","pmid":"38900911","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":[]}