{"doi":"10.1242/jcs.260944","title":"The histone H3/H4 chaperone CHAF1B prevents the mislocalization of CENP-A for chromosomal stability","abstract":"Restricting the localization of the evolutionarily conserved centromeric histone H3 variant CENP-A to centromeres prevents chromosomal instability (CIN). The mislocalization of CENP-A to non-centromeric regions contributes to CIN in yeasts, flies and human cells. Even though overexpression and mislocalization of CENP-A have been reported in cancers, the mechanisms responsible for its mislocalization remain poorly understood. Here, we used an imaging-based high-throughput RNAi screen to identify factors that prevent mislocalization of overexpressed YFP-tagged CENP-A (YFP-CENP-A) in HeLa cells. Among the top five candidates in the screen - the depletion of which showed increased nuclear YFP-CENP-A fluorescence - were the histone chaperones CHAF1B (or p60) and CHAF1A (or p150). Follow-up validation and characterization experiments showed that CHAF1B-depleted cells exhibited CENP-A mislocalization, CIN phenotypes and increased enrichment of CENP-A in chromatin fractions. The depletion of DAXX, a histone H3.3 chaperone, suppressed CENP-A mislocalization and CIN in CHAF1B-depleted cells. We propose that in CHAF1B-depleted cells, DAXX promotes mislocalization of the overexpressed CENP-A to non-centromeric regions, resulting in CIN. In summary, we identified regulators of CENP-A localization and defined a role for CHAF1B in preventing DAXX-dependent CENP-A mislocalization and CIN.","journal":"Journal of Cell Science","year":2023,"id":339658,"datarank":0.6083024458140787,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.18332044420564617,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.18332044420564617,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":9,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":true,"deposit_databanks":{"figshare":["10.6084/m9.figshare.22704505.v2"]},"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":1074137,"name":"Vinutha Balachandra","orcid":null,"position":1,"is_corresponding":false},{"id":946450,"name":"J. Kim","orcid":"0000-0003-0304-3738","position":2,"is_corresponding":false},{"id":656255,"name":"Austin Rossi","orcid":null,"position":3,"is_corresponding":false},{"id":550904,"name":"Pranathi Vadlamani","orcid":"0000-0003-4526-9567","position":4,"is_corresponding":false},{"id":1074138,"name":"Subhash Chandra Sethi","orcid":null,"position":5,"is_corresponding":false},{"id":89254,"name":"Laurent Ozbun","orcid":"0000-0002-0862-3929","position":6,"is_corresponding":false},{"id":1074139,"name":"Shinjen Lin","orcid":null,"position":7,"is_corresponding":false},{"id":1074140,"name":"Ken Chin-Chien Cheng","orcid":null,"position":8,"is_corresponding":false},{"id":260578,"name":"Raj Chari","orcid":"0000-0002-2216-313X","position":9,"is_corresponding":false},{"id":516352,"name":"Tatiana Karpova","orcid":"0000-0001-6025-2128","position":10,"is_corresponding":false},{"id":404288,"name":"Gianluca Pegoraro","orcid":"0000-0003-2843-9464","position":11,"is_corresponding":false},{"id":655613,"name":"Daniel R. Foltz","orcid":"0000-0001-7423-6188","position":12,"is_corresponding":false},{"id":496129,"name":"Natasha J. Caplen","orcid":"0000-0002-0001-9460","position":13,"is_corresponding":false},{"id":597267,"name":"Munira A. Basrai","orcid":"0000-0001-9660-9299","position":14,"is_corresponding":false},{"id":1073032,"name":"Roshan L. Shrestha","orcid":"0000-0001-7597-9418","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:10:49.535464Z","pmid":"37129573","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":[]}