{"doi":"10.1038/s41556-024-01565-x","title":"Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint","abstract":"Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear. Here, using a tunable system of chromosome mis-segregation, we show that mitotic errors trigger nuclear deformation, nuclear softening, and lamin and heterochromatin alterations, leading to rapid p53/p21 activation upon mitotic exit in response to changes in nuclear mechanics. We identify mTORC2 and ATR as nuclear deformation sensors upstream of p53/p21 activation. While triggering mitotic arrest, the chromosome mis-segregation-induced alterations of nuclear envelope mechanics provide a fitness advantage for aneuploid cells by promoting nuclear deformation resilience and enhancing pro-invasive capabilities. Collectively, this work identifies a nuclear mechanical checkpoint triggered by altered chromatin organization that probably plays a critical role in cellular transformation and cancer progression. Hervé, Scelfo et al. show that chromosome mis-segregation induces mTORC2- and ATR-mediated p53 activation through a mechanosensitive checkpoint at the nuclear envelope triggered by altered heterochromatin content and increased nuclear membrane tension.","journal":"Nature Cell Biology","year":2025,"id":509293,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":559431,"name":"Andrea Scelfo","orcid":"0000-0001-8767-0688","position":1,"is_corresponding":false},{"id":1364066,"name":"Gabriele Bersano Marchisio","orcid":null,"position":2,"is_corresponding":false},{"id":1364067,"name":"Marine Grison","orcid":null,"position":3,"is_corresponding":false},{"id":1363188,"name":"Kotryna Vaidžiulytė","orcid":"0000-0002-2114-3612","position":4,"is_corresponding":false},{"id":472664,"name":"Marie Dumont","orcid":"0000-0002-0636-0731","position":5,"is_corresponding":false},{"id":1363189,"name":"Annapaola Angrisani","orcid":"0000-0002-3407-7669","position":6,"is_corresponding":false},{"id":304379,"name":"Adib Keikhosravi","orcid":"0000-0002-7901-1276","position":7,"is_corresponding":false},{"id":404288,"name":"Gianluca Pegoraro","orcid":"0000-0003-2843-9464","position":8,"is_corresponding":false},{"id":1363190,"name":"Mathieu Deygas","orcid":"0000-0003-3417-8133","position":9,"is_corresponding":false},{"id":225162,"name":"G. Nader","orcid":"0000-0002-1905-1903","position":10,"is_corresponding":false},{"id":207334,"name":"Anne‐Sophie Macé","orcid":"0000-0003-3072-3819","position":11,"is_corresponding":false},{"id":28893,"name":"Matteo Gentili","orcid":"0000-0002-6970-8133","position":12,"is_corresponding":false},{"id":1363191,"name":"Alice Williart","orcid":"0000-0003-2581-0379","position":13,"is_corresponding":false},{"id":225171,"name":"Nicolas Manel","orcid":"0000-0002-1481-4430","position":14,"is_corresponding":false},{"id":225174,"name":"Matthieu Piel","orcid":"0000-0002-2848-177X","position":15,"is_corresponding":false},{"id":109764,"name":"Yekaterina A. Miroshnikova","orcid":"0000-0001-9771-4963","position":16,"is_corresponding":false},{"id":472667,"name":"Daniele Fachinetti","orcid":"0000-0002-8795-6771","position":17,"is_corresponding":false},{"id":472666,"name":"Solène Hervé","orcid":"0000-0002-5015-8493","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:47:24.513904Z","pmid":"39779939","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":[]}