{"doi":"10.1101/2021.03.30.437768","title":"Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis","abstract":"Abstract In addition to its classical role in apoptosis, accumulating evidence suggests that caspase-2 has non-apoptotic functions, including regulation of cell division. Loss of caspase-2 is known to increase proliferation rates but how caspase-2 is regulating this process is currently unclear. We show that caspase-2 is activated in dividing cells in G1- and early S-phase. In the absence of caspase-2, cells exhibit numerous S-phase defects including delayed exit from S-phase, S-phase-associated chromosomal aberrations, and increased DNA damage following S-phase arrest. In addition, caspase-2-deficient cells have a higher frequency of stalled replication forks, decreased DNA fiber length, and impeded progression of DNA replication tracts. This indicates that caspase-2 reduces replication stress and promotes replication fork protection to maintain genomic stability. These functions are independent of the pro-apoptotic function of caspase-2 because blocking caspase-2-induced cell death had no effect on cell division or DNA damage-induced cell cycle arrest. Thus, our data supports a model where caspase-2 regulates cell cycle events to protect from the accumulation of DNA damage independently of its pro-apoptotic function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":223780,"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":0.9581,"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":667023,"name":"Raj K. Pandita","orcid":null,"position":1,"is_corresponding":false},{"id":638912,"name":"Karla E. Rojas López","orcid":"0000-0001-7301-5260","position":2,"is_corresponding":false},{"id":825576,"name":"Melissa J. Parsons","orcid":"0000-0002-2131-9577","position":3,"is_corresponding":false},{"id":574285,"name":"Chloé I. Charendoff","orcid":null,"position":4,"is_corresponding":false},{"id":667024,"name":"Vijay Charaka","orcid":null,"position":5,"is_corresponding":false},{"id":245874,"name":"Alexandre F. Carisey","orcid":"0000-0003-1326-2205","position":6,"is_corresponding":false},{"id":753581,"name":"Tej K. Pandita","orcid":"0000-0002-1399-808X","position":7,"is_corresponding":false},{"id":230333,"name":"Lisa Bouchier‐Hayes","orcid":"0000-0003-3886-5977","position":8,"is_corresponding":false},{"id":233999,"name":"Ashley Boice","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:54:14.760456Z","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":[]}