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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Annexin A2 / metabolism
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Cell Cycle / genetics*
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Cell Cycle Proteins / metabolism
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Cell Line
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Centromere / genetics
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Centromere / metabolism*
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Centromere Protein A
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Chromosomal Proteins, Non-Histone / metabolism
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Chromosome Segregation
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Cyclin A / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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Epigenesis, Genetic
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Genome-Wide Association Study*
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Histones / genetics
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Histones / metabolism*
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Mitosis / genetics
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Mutation
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RNA Interference*
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S100 Proteins / metabolism
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Ubiquitin-Protein Ligase Complexes / metabolism
Substances
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Annexin A2
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Cell Cycle Proteins
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Centromere Protein A
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Chromosomal Proteins, Non-Histone
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Cid protein, Drosophila
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Cyclin A
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DNA-Binding Proteins
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Drosophila Proteins
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Histones
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Rca1 protein, Drosophila
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S100 Proteins
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S100 calcium binding protein A10
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centromere protein C
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome