{"doi":"10.17615/2a21-f958","title":"CDK1-dependent Inhibition of the E3 Ubiquitin Ligase CRL4 CDT2 Ensures Robust Transition from S Phase to Mitosis","abstract":"Replication-coupled destruction of a cohort of cell cycle proteins ensures efficient and precise genome duplication. Three proteins destroyed during replication via the CRL4CDT2 ubiquitin E3 ligase, CDT1, p21, and SET8 (PR-SET7), are also essential or important during mitosis, making their reaccumulation after S phase a critical cell cycle event. During early and mid-S phase and during DNA repair, proliferating cell nuclear antigen (PCNA) loading onto DNA (PCNADNA) triggers the interaction between CRL4CDT2 and its substrates, resulting in their degradation. We have discovered that, beginning in late S phase, PCNADNA is no longer sufficient to trigger CRL4CDT2-mediated degradation. A CDK1-dependent mechanism that blocks CRL4CDT2 activity by interfering with CDT2 recruitment to chromatin actively protects CRL4CDT2 substrates. We postulate that deliberate override of replication-coupled destruction allows anticipatory accumulation in late S phase. We further show that (as for CDT1) de novo SET8 reaccumulation is important for normal mitotic progression. In this manner, CDK1-dependent CRL4CDT2 inactivation contributes to efficient transition from S phase to mitosis.","journal":"UNC Libraries","year":2020,"id":142993,"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":0.942,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":610059,"name":"Kate E. Coleman","orcid":"0000-0003-4676-4981","position":1,"is_corresponding":false},{"id":266825,"name":"Jeanette Gowen Cook","orcid":"0000-0003-0849-7405","position":2,"is_corresponding":false},{"id":29392,"name":"Lindsay F. Rizzardi","orcid":"0000-0002-2866-9625","position":3,"is_corresponding":false},{"id":430590,"name":"Jacob P. Matson","orcid":"0000-0002-9375-1676","position":4,"is_corresponding":false},{"id":484251,"name":"Seeun Oh","orcid":"0000-0003-0717-4073","position":5,"is_corresponding":false},{"id":598719,"name":"Dileep Varma","orcid":"0000-0002-0972-8669","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:34.768426Z","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":[]}