title: C. elegans mitotic cyclins have distinct as well as overlapping functions in chromosome segregation.
abstract: Mitotic cyclins in association with the Cdk1 protein kinase regulate progression through mitosis in all eukaryotes. Here, we address to what extent mitotic cyclins in the nematode Caenorhabditis elegans provide overlapping functions or distinct biological activities. C. elegans expresses a single A-type cyclin (CYA-1), three typical B-type cyclins (CYB-1, CYB-2.1 and CYB-2.2), and one B3-subfamily member (CYB-3). While we observed clear redundancies between the cyb genes, cyb-1 and cyb-3 also contribute specific essential functions in meiosis and mitosis. CYB-1 and CYB-3 show similar temporal and spatial expression, both cyclins localize prominently to the nucleus, and both associate with CDK-1 and display histone H1 kinase activity in vitro. We demonstrate that inhibition of cyb-1 by RNAi interferes with chromosome congression and causes aneuploidy. In contrast, cyb-3(RNAi) embryos fail to initiate sister chromatid separation. Inhibition of both cyclins simultaneously results in a much earlier and more dramatic arrest. However, only the combination of cyb-1, cyb-3 and cyb-2.1/cyb-2.2 RNAi fully resembles cdk-1 inhibition. This combination of redundant and specific phenotypes supports that in vivo phosphorylation of certain Cdk targets can be achieved by multiple Cdk1/cyclin complexes, while phosphorylation of other targets requires a unique Cdk1/cyclin combination.
authors.affiliation: Developmental Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van der Voet
authors.forename: Monique A
authors.initials: MA
authors.lastname: Lorson
authors.forename: Dayalan G
authors.initials: DG
authors.lastname: Srinivasan
authors.forename: Karen L
authors.initials: KL
authors.lastname: Bennett
authors.forename: Sander
authors.initials: S
authors.lastname: van den Heuvel
mesh_terms: D000782:Aneuploidy; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics*; D056750:Cyclin A1 / Q000235:genetics; D019926:Cyclin B / Q000235:genetics; D056744:Cyclin B1 / Q000235:genetics; D056765:Cyclin B2 / Q000235:genetics; D016213:Cyclins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D019143:Evolution, Molecular; D018816:Genes, cdc / Q000502:physiology; D046911:Macromolecular Substances / Q000378:metabolism; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010802:Phylogeny; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid
chemical_list: D056750:Cyclin A1; D019926:Cyclin B; D056744:Cyclin B1; D056765:Cyclin B2; D016213:Cyclins; D029721:Drosophila Proteins; D046911:Macromolecular Substances; C539905:cyclin B3, Drosophila; D016203:CDC2 Protein Kinase