{"doi":"10.1016/j.celrep.2023.112428","title":"Fanconi anemia-associated chromosomal radial formation is dependent on POLθ-mediated alternative end joining","abstract":"Activation of the Fanconi anemia (FA) pathway after treatment with mitomycin C (MMC) is essential for preventing chromosome translocations termed \"radials.\" When replication forks stall at MMC-induced interstrand crosslinks (ICLs), the FA pathway is activated to orchestrate ICL unhooking and repair of the DNA break intermediates. However, in FA-deficient cells, how ICL-associated breaks are resolved in a manner that leads to radials is unclear. Here, we demonstrate that MMC-induced radials are dependent on DNA polymerase theta (POLθ)-mediated alternative end joining (A-EJ). Specifically, we show that radials observed in FANCD2 −/− cells are dependent on POLθ and DNA ligase III and occur independently of classical non-homologous end joining. Furthermore, treatment of FANCD2 −/− cells with POLθ inhibitors abolishes radials and leads to the accumulation of breaks co-localizing with common fragile sites. Uniformly, these observations implicate A-EJ in radial formation and provide mechanistic insights into the treatment of FA pathway-deficient cancers with POLθ inhibitors.","journal":"Cell Reports","year":2023,"id":347700,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1090043,"name":"Rachel E. Kram","orcid":null,"position":1,"is_corresponding":false},{"id":261893,"name":"Kevin Lin","orcid":"0000-0002-1236-9847","position":2,"is_corresponding":false},{"id":52090,"name":"Chad L. Myers","orcid":"0000-0002-1026-5972","position":3,"is_corresponding":false},{"id":1070263,"name":"Alexandra Sobeck","orcid":null,"position":4,"is_corresponding":false},{"id":365949,"name":"Eric A. Hendrickson","orcid":"0000-0001-6734-6426","position":5,"is_corresponding":false},{"id":263507,"name":"Anja‐Katrin Bielinsky","orcid":"0000-0003-1783-619X","position":6,"is_corresponding":false},{"id":683938,"name":"Colette B. Rogers","orcid":"0000-0001-9830-2215","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:12:01.859977Z","pmid":"37086407","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":[]}