{"doi":"10.1101/2021.02.02.429360","title":"Chromatin Bridges, not Micronuclei, Activate cGAS after Drug-induced Mitotic Errors in Human Cells","abstract":"Summary Mitotic errors can activate cGAS and induce type-I interferon (IFN) signaling. Current models propose that chromosome segregation errors generate micronuclei whose rupture activates cGAS. We used a panel of anti-mitotic drugs to perturb mitosis in fibroblasts and measured abnormal nuclear morphologies, cGAS localization and IFN signaling in the subsequent interphase. Micronuclei consistently recruited cGAS without activating it. Instead, IFN signaling correlated with formation of cGAS-coated chromatin bridges that were selectively generated by microtubule stabilizers and MPS1 inhibitors. cGAS activation by chromatin bridges was suppressed by drugs that prevented cytokinesis. We confirmed cGAS activation by chromatin bridges in cancer lines that are unable to secrete IFN by measuring paracrine transfer of 2′3-cGAMP to fibroblasts. We propose that cGAS is selectively activated by self-chromatin when it is stretched in chromatin bridges. Immunosurveillance of cells that fail mitosis, and anti-tumor actions of taxanes and MPS1 inhibitors, may depend on this effect.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":214714,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":506393,"name":"Peter D. Koch","orcid":"0000-0001-8312-1657","position":1,"is_corresponding":false},{"id":362447,"name":"Timothy J. Mitchison","orcid":"0000-0001-7781-1897","position":2,"is_corresponding":false},{"id":808349,"name":"Patrick Flynn","orcid":"0000-0003-4693-9681","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:46.604690Z","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":[]}