title: RbAp46/48(LIN-53) Is Required for Holocentromere Assembly in Caenorhabditis elegans.
abstract: Centromeres, the specialized chromosomal regions for recruiting kinetochores and directing chromosome segregation, are epigenetically marked by a centromeric histone H3 variant, CENP-A. To maintain centromere identity through cell cycles, CENP-A diluted during DNA replication is replenished. The licensing factor M18BP1(KNL-2) is known to recruit CENP-A to holocentromeres. Here, we show that RbAp46/48(LIN-53), a conserved histone chaperone, is required for CENP-A(HCP-3) localization in holocentric Caenorhabditis elegans. Indeed, RbAp46/48(LIN-53) and CENP-A(HCP-3) localizations are interdependent. RbAp46/48(LIN-53) localizes to the centromere during metaphase in a CENP-A(HCP-3)- and M18BP1(KNL-2)-dependent manner, suggesting CENP-A(HCP-3) loading may occur before anaphase. RbAp46/48(LIN-53) does not function at the centromere through histone acetylation, H3K27 trimethylation, or its known chromatin-modifying complexes. RbAp46/48(LIN-53) may function independently to escort CENP-A(HCP-3) for holocentromere assembly but is dispensable for other kinetochore protein recruitment. Nonetheless, depletion of RbAp46/48(LIN-53) leads to anaphase bridges and chromosome missegregation. This study unravels the holocentromere assembly hierarchy and its conservation with monocentromeres.
authors.affiliation: School of Biological Sciences, the University of Hong Kong, Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong.
authors.forename: Bernard Chi Hang
authors.initials: BC
authors.lastname: Lee
authors.affiliation: School of Biological Sciences, the University of Hong Kong, Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Lin
authors.affiliation: School of Biological Sciences, the University of Hong Kong, Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong. Electronic address: kwyyuen@hku.hk.
authors.forename: Karen Wing Yee
authors.initials: KW
authors.lastname: Yuen
mesh_terms: D000705:Anaphase; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002503:Centromere / Q000378:metabolism* / Q000648:ultrastructure; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D004261:DNA Replication; D004625:Embryo, Nonmammalian; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008677:Metaphase; D021381:Protein Transport; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001324:Autoantigens; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C116486:LIN-53 protein, C elegans; D012097:Repressor Proteins