cdk-7 Is required for mRNA transcription and cell cycle progression in Caenorhabditis elegans embryos.
CDK7 is a cyclin-dependent kinase proposed to function in two essential cellular processes: transcription and cell cycle regulation. CDK7 is the kinase subunit of the general transcription factor TFIIH that phosphorylates the C-terminal domain (CTD) of RNA polymerase II, and has been shown to be broadly required for transcription in Saccharomyces cerevisiae. CDK7 can also phosphorylate CDKs that promote cell cycle progression, and has been shown to function as a CDK-activating kinase (CAK) in Schizosaccharomyces pombe and Drosophila melanogaster. That CDK7 performs both functions in metazoans has been difficult to prove because transcription is essential for cell cycle progression in most cells. We have isolated a temperature-sensitive mutation in Caenorhabditis elegans cdk-7 and have used it to analyze the role of cdk-7 in embryonic blastomeres, where cell cycle progression is independent of transcription. Partial loss of cdk-7 activity leads to a general decrease in CTD phosphorylation and embryonic transcription, and severe loss of cdk-7 activity blocks all cell divisions. Our results support a dual role for metazoan CDK7 as a broadly required CTD kinase, and as a CAK essential for cell cycle progression.
Wallenfang
Matthew R
MR
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Seydoux
Geraldine
G
D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D002453:Cell Cycle; D002460:Cell Line; D019070:Cell Lineage; D003001:Cloning, Molecular; D018844:Cyclin-Dependent Kinases; D049452:Green Fluorescent Proteins; D017403:In Situ Hybridization; D008164:Luminescent Proteins / Q000378:metabolism; D008540:Meiosis; D018715:Microscopy, Video; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011003:Ploidies; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013696:Temperature; D014158:Transcription, Genetic; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D008164:Luminescent Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II; D000095043:Cyclin-Dependent Kinase-Activating Kinase