{"doi":"10.1093/nar/gkac304","title":"SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination","abstract":"Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis.","journal":"Nucleic Acids Research","year":2022,"id":242285,"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":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":687118,"name":"Huijuan Lin","orcid":null,"position":1,"is_corresponding":false},{"id":244165,"name":"N. Adrian Leu","orcid":null,"position":2,"is_corresponding":false},{"id":301515,"name":"Gordon Ruthel","orcid":"0000-0001-9193-5589","position":3,"is_corresponding":false},{"id":276936,"name":"Serge Y. Fuchs","orcid":"0000-0002-0136-5103","position":4,"is_corresponding":false},{"id":276935,"name":"Luca Busino","orcid":"0000-0001-6758-9276","position":5,"is_corresponding":false},{"id":686140,"name":"Mengcheng Luo","orcid":"0000-0001-7058-5911","position":6,"is_corresponding":false},{"id":316417,"name":"P. Jeremy Wang","orcid":"0000-0003-2311-4089","position":7,"is_corresponding":false},{"id":747288,"name":"Yongjuan Guan","orcid":"0000-0001-8981-0736","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T00:23:05.485568Z","pmid":"35489071","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":[]}