{"doi":"10.1126/science.adi2421","title":"CDK4/6 activity is required during G <sub>2</sub> arrest to prevent stress-induced endoreplication","abstract":"Cell cycle events are coordinated by cyclin-dependent kinases (CDKs) to ensure robust cell division. CDK4/6 and CDK2 regulate the growth 1 (G 1 ) to synthesis (S) phase transition of the cell cycle by responding to mitogen signaling, promoting E2F transcription and inhibition of the anaphase-promoting complex. We found that this mechanism was still required in G 2 -arrested cells to prevent cell cycle exit after the S phase. This mechanism revealed a role for CDK4/6 in maintaining the G 2 state, challenging the notion that the cell cycle is irreversible and that cells do not require mitogens after passing the restriction point. Exit from G 2 occurred during ribotoxic stress and was actively mediated by stress-activated protein kinases. Upon relief of stress, a significant fraction of cells underwent a second round of DNA replication that led to whole-genome doubling.","journal":"Science","year":2024,"id":420431,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":1211369,"name":"Yovel Lendner","orcid":"0000-0002-7506-854X","position":1,"is_corresponding":false},{"id":1166166,"name":"Adler Guerrero Zuniga","orcid":"0000-0002-5095-9493","position":2,"is_corresponding":false},{"id":247995,"name":"Niladri K. Sinha","orcid":"0000-0002-9143-495X","position":3,"is_corresponding":false},{"id":1211820,"name":"Benjamin Veresko","orcid":null,"position":4,"is_corresponding":false},{"id":1211370,"name":"Timothy J. Aikin","orcid":"0000-0003-4594-1691","position":5,"is_corresponding":false},{"id":225954,"name":"Sergi Regot","orcid":"0000-0001-9786-3897","position":6,"is_corresponding":false},{"id":699502,"name":"Connor McKenney","orcid":"0000-0002-2231-5180","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:57:25.777459Z","pmid":"38696576","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":[]}