A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis.
In a screen for genes that interact with the Rap1 GTPase, we have identified a Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk inhibitors. Unlike mammalian cdk inhibitors studied to date, dap is essential for normal embryonic development. Dacapo inhibits cyclin-cdk activity in vitro. Overexpressing dap during eye development interferes with cell cycle progression and interacts genetically with the retinoblastoma homolog (Rbf) and cyclin E. dap expression in embryos parallels the exit of cells from the cell cycle. dap mutant embryos delay the normal cell cycle exit during development; many cells complete an additional cycle and subsequently become quiescent. Thus, dap functions during embryogenesis to achieve a precisely timed exit from the cell cycle.
de Nooij
J C
JC
Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.
Letendre
M A
MA
Hariharan
I K
IK
D000595:Amino Acid Sequence; D000818:Animals; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D003001:Cloning, Molecular; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000037:antagonists & inhibitors*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology; D004791:Enzyme Inhibitors; D000078404:Epidermal Cells; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D005804:Genes, Lethal; D006131:Growth Inhibitors; D019476:Insect Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment
D016213:Cyclins; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D019476:Insect Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C103336:dap protein, Drosophila; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C495887:cdk2 protein, Drosophila