title: CRL4(RBBP7) is required for efficient CENP-A deposition at centromeres.
abstract: The mitotic spindle drives chromosome movement during mitosis and attaches to chromosomes at dedicated genomic loci named centromeres. Centromeres are epigenetically specified by their histone composition, namely the presence of the histone H3 variant CENP-A, which is regulated during the cell cycle by its dynamic expression and localization. Here, we combined biochemical methods and quantitative imaging approaches to investigate a new function of CUL4-RING E3 ubiquitin ligases (CRL4) in regulating CENP-A dynamics. We found that the core components CUL4 and DDB1 are required for centromeric loading of CENP-A, but do not influence CENP-A maintenance or pre-nucleosomal CENP-A levels. Interestingly, we identified RBBP7 as a substrate-specific CRL4 adaptor required for this process, in addition to its role in binding and stabilizing soluble CENP-A. Our data thus suggest that the CRL4 complex containing RBBP7 (CRL4(RBBP7)) might regulate mitosis by promoting ubiquitin-dependent loading of newly synthesized CENP-A during the G1 phase of the cell cycle.
authors: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
authors: Julien
authors: J
authors: Mouysset
authors: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
authors: Samuel
authors: S
authors: Gilberto
authors: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland Department of Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors: Michelle G
authors: MG
authors: Meier
authors: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
authors: Fabienne
authors: F
authors: Lampert
authors: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
authors: Mukta
authors: M
authors: Belwal
authors: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland Department of Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
authors: Patrick
authors: P
authors: Meraldi
authors: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland matthias.peter@bc.biol.ethz.ch.
authors: Matthias
authors: M
authors: Peter
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D011485:Protein Binding; D055550:Protein Stability; D056505:Retinoblastoma-Binding Protein 4 / Q000378:metabolism; D056524:Retinoblastoma-Binding Protein 7 / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; C091435:DDB1 protein, human; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; C082637:RBBP4 protein, human; C490746:RBBP7 protein, human; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7
keywords: CENP‐A; Centromere; Cullin; RBBP7