{"doi":"10.1101/2023.05.10.539634","title":"Defining a core configuration for human centromeres during mitosis","abstract":"The biorientation of sister chromatids on the mitotic spindle, essential for accurate sister chromatid segregation, relies on critical centromere components including cohesin, the centromere-specific H3 variant CENP-A, and centromeric DNA. Centromeric DNA is highly variable between chromosomes yet must accomplish a similar function. Moreover, how the 50 nm cohesin ring, proposed to encircle sister chromatids, accommodates inter-sister centromeric distances of hundreds of nanometers on the metaphase spindle is a conundrum. Insight into the 3D organization of centromere components would help resolve how centromeres function on the mitotic spindle. We used ChIP-seq and super-resolution microscopy to examine the geometry of essential centromeric components on human chromosomes. ChIP-seq demonstrates that cohesin subunits are depleted in α-satellite arrays where CENP-A nucleosomes and kinetochores assemble. Cohesin is instead enriched at pericentromeric DNA. Structured illumination microscopy of sister centromeres is consistent, revealing a non-overlapping pattern of CENP-A and cohesin. We used single particle averaging of hundreds of mitotic sister chromatids to develop an average centromere model. CENP-A clusters on sister chromatids, connected by α-satellite, are separated by ~562 nm with a perpendicular intervening ~190 nM wide axis of cohesin. Two differently sized α-satellite arrays on chromosome 7 display similar inter-sister CENP-A cluster distance, demonstrating different sized arrays can achieve a common spacing. Our data suggest a working model for a common core configuration of essential centromeric components that includes CENP-A nucleosomes at the outer edge of extensible α-satellite DNA and pericentromeric cohesion. This configuration helps reconcile how centromeres function and serves as a foundation for future studies of additional components required for centromere function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399313,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9459,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":561792,"name":"Chris Seidel","orcid":"0000-0001-9218-7922","position":1,"is_corresponding":false},{"id":560927,"name":"Dai Tsuchiya","orcid":"0000-0001-8385-2775","position":2,"is_corresponding":false},{"id":51352,"name":"Sean McKinney","orcid":"0000-0002-9740-6247","position":3,"is_corresponding":false},{"id":376552,"name":"Zulin Yu","orcid":"0000-0002-1292-8426","position":4,"is_corresponding":false},{"id":560928,"name":"Sarah E. Smith","orcid":"0000-0003-1570-5700","position":5,"is_corresponding":false},{"id":539553,"name":"Jay R. Unruh","orcid":"0000-0003-3077-4990","position":6,"is_corresponding":false},{"id":108065,"name":"Jennifer L. Gerton","orcid":"0000-0003-0743-3637","position":7,"is_corresponding":false},{"id":1069767,"name":"Ayantika Sen Gupta","orcid":"0000-0002-6920-0356","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:19:51.724387Z","pmid":"37214893","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":[]}