title: Genome-wide analysis reveals a cell cycle-dependent mechanism controlling centromere propagation.
abstract: Centromeres are the structural and functional foundation for kinetochore formation, spindle attachment, and chromosome segregation. In this study, we isolated factors required for centromere propagation using genome-wide RNA interference screening for defects in centromere protein A (CENP-A; centromere identifier [CID]) localization in Drosophila melanogaster. We identified the proteins CAL1 and CENP-C as essential factors for CID assembly at the centromere. CID, CAL1, and CENP-C coimmunoprecipitate and are mutually dependent for centromere localization and function. We also identified the mitotic cyclin A (CYCA) and the anaphase-promoting complex (APC) inhibitor RCA1/Emi1 as regulators of centromere propagation. We show that CYCA is centromere localized and that CYCA and RCA1/Emi1 couple centromere assembly to the cell cycle through regulation of the fizzy-related/CDH1 subunit of the APC. Our findings identify essential components of the epigenetic machinery that ensures proper specification and propagation of the centromere and suggest a mechanism for coordinating centromere inheritance with cell division.
authors.affiliation: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Erhardt
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Mellone
authors.forename: Craig M
authors.initials: CM
authors.lastname: Betts
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
authors.forename: Gary H
authors.initials: GH
authors.lastname: Karpen
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Straight
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002503:Centromere / Q000235:genetics / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D019925:Cyclin A / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D034622:RNA Interference; D009418:S100 Proteins / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D000099248:S100 Calcium Binding Protein A10
chemical_list: D064173:Anaphase-Promoting Complex-Cyclosome; D017306:Annexin A2; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D019925:Cyclin A; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D009418:S100 Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D000099248:S100 Calcium Binding Protein A10; C427237:Cid protein, Drosophila; C491136:Rca1 protein, Drosophila; C060905:centromere protein C