{"doi":"10.1101/2025.10.20.683541","title":"Scm3 interacts with the N-terminal tail of Cse4 to regulate kinetochore assembly in budding yeast","abstract":"Abstract The kinetochore is a multiprotein complex formed at the centromeres and is essential for the faithful chromosome segregation. In most of the organisms the kinetochore is assembled on a specialized centromeric nucleosome where histone H3 is replaced by a variant, named CENP-A. In budding yeast, the CENP-A homolog, Cse4 is recruited to the centromeric nucleosome through an interaction between its C-terminal domain and a specific chaperone, named Scm3. Interestingly, following Cse4 recruitment during S phase, Scm3 persists at the centromeres throughout the cell cycle. Recent in vitro studies have reported that Scm3 also interacts with N-terminal of Cse4 (N-C) that in turn facilitates a better interaction of Ame1-Okp1 (AO) of COMA subcomplex with N-C, which promotes kinetochore assembly. In this work, using genetic and biochemical assays we provide in vivo evidence of the interaction between Scm3 and N-C. Additionally, by artificially tethering Scm3, we show that their association has the potential to stabilize a missegregating chromosome with inactive centromere, perhaps by forming an active kinetochore at an ectopic site. We propose that at the centromeres, Scm3 has two jobs in tandem - Cse4 deposition and stabilization of N-C, which together culminates into proper kinetochore assembly. This work has clinical significance as both CENP-A and its chaperone are known to be upregulated in human cells under disease states which can predispose the cells to aneuploidy due to increased chances of forming ectopic kinetochores.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556843,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"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":1456523,"name":"Anushka Alekar","orcid":"0009-0002-8032-3397","position":1,"is_corresponding":false},{"id":1456956,"name":"Shubhomita Mallick","orcid":"0009-0002-2169-7479","position":2,"is_corresponding":false},{"id":416355,"name":"Jagesh V. Shah","orcid":"0009-0001-1427-6177","position":3,"is_corresponding":false},{"id":380263,"name":"Munira A. Basrai","orcid":"0000-0003-0628-8052","position":4,"is_corresponding":false},{"id":1456524,"name":"Santanu Ghosh","orcid":"0000-0002-3190-8084","position":5,"is_corresponding":false},{"id":1456522,"name":"Prakhar Agarwal","orcid":"0000-0001-5794-545X","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:13.130091Z","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":[]}