{"doi":"10.17615/6751-sp75","title":"Mechanism of Replication-Coupled DNA Interstrand Crosslink Repair","abstract":"DNA interstrand cross-links (ICLs) are toxic DNA lesions whose repair occurs in the S phase of metazoans via an unknown mechanism. Here, we describe a novel cell-free system based on Xenopus egg extracts that supports ICL repair. During DNA replication of a plasmid containing a site-specific ICL, two replication forks converge on the cross-link. Subsequent lesion bypass involves advance of a nascent leading strand to within one nucleotide of the ICL, followed by incisions, translesion DNA synthesis, and extension of the nascent strand beyond the lesion. Immunodepletion experiments suggest that extension requires DNA polymeras ζ Ultimately, a significant portion of the input DNA is fully repaired, but not if DNA replication is blocked. Repair in this system is accompanied by activation of the Fanconi anemia and ATR checkpoint pathways. Our experiments establish a mechanism for ICL repair that reveals how this process is coupled to DNA replication.","journal":"Carolina Digital Repository (University of North Carolina at Chapel Hill)","year":2020,"id":137718,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307697,"name":"Jack D. Griffith","orcid":"0000-0002-8357-8689","position":1,"is_corresponding":false},{"id":598379,"name":"T. Angelov","orcid":"0000-0003-4318-6864","position":2,"is_corresponding":false},{"id":251359,"name":"Johannes C. Walter","orcid":"0000-0002-4186-7570","position":3,"is_corresponding":false},{"id":354400,"name":"Orlando D. Schärer","orcid":"0000-0003-2425-2715","position":4,"is_corresponding":false},{"id":598959,"name":"Puck Knipsheer","orcid":null,"position":5,"is_corresponding":false},{"id":598380,"name":"Jingchuan Sun","orcid":"0000-0002-8956-9409","position":6,"is_corresponding":false},{"id":598960,"name":"Milica Enoiu","orcid":null,"position":7,"is_corresponding":false},{"id":177912,"name":"Tom Ellenberger","orcid":null,"position":8,"is_corresponding":false},{"id":598378,"name":"Markus Räschle","orcid":"0000-0002-6737-7203","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:59.449905Z","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":[]}