The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for M phase in meiotic and mitotic cell divisions, but not for S phase.
We have identified six protein kinases that belong to the family of cdc2-related kinases in Caenorhabditis elegans. Results from RNA interference experiments indicate that at least one of these kinases is required for cell-cycle progression during meiosis and mitosis. This kinase, encoded by the ncc-1 gene, is closely related to human Cdk1/Cdc2, Cdk2 and Cdk3 and yeast CDC28/cdc2(+). We addressed whether ncc-1 acts to promote passage through a single transition or multiple transitions in the cell cycle, analogous to Cdks in vertebrates or yeasts, respectively. We isolated five recessive ncc-1 mutations in a genetic screen for mutants that resemble larval arrested ncc-1(RNAi) animals. Our results indicate that maternal ncc-1 product is sufficient for embryogenesis, and that zygotic expression is required for cell divisions during larval development. Cells that form the postembryonic lineages in wild-type animals do not enter mitosis in ncc-1 mutants, as indicated by lack of chromosome condensation and nuclear envelope breakdown. However, progression through G1 and S phase appears unaffected, as revealed by expression of ribonucleotide reductase, incorporation of BrdU and DNA quantitation. Our results indicate that C. elegans uses multiple Cdks to regulate cell-cycle transitions and that ncc-1 is the C. elegans ortholog of Cdk1/Cdc2 in other metazoans, required for M phase in meiotic as well as mitotic cell cycles.
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Massachusetts General Hospital Cancer Center, Building 149, Charlestown, MA 02129, USA.
Srinivasan
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van den Heuvel
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D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics* / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D004261:DNA Replication; D015870:Gene Expression; D017238:Genes, Helminth; D016679:Genome, Viral; D005854:Germ Cells; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007814:Larva; D008540:Meiosis; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D010641:Phenotype; D018510:RNA, Helminth
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D015801:Helminth Proteins; D018510:RNA, Helminth; C119681:cdk-1 protein, C elegans; D016203:CDC2 Protein Kinase