title: Interlocked feedback loops within the Drosophila circadian oscillator.
abstract: Drosophila Clock (dClk) is rhythmically expressed, with peaks in mRNA and protein (dCLK) abundance early in the morning. dClk mRNA cycling is shown here to be regulated by PERIOD-TIMELESS (PER-TIM)-mediated release of dCLK- and CYCLE (CYC)-dependent repression. Lack of both PER-TIM derepression and dCLK-CYC repression results in high levels of dClk mRNA, which implies that a separate dClk activator is present. These results demonstrate that the Drosophila circadian feedback loop is composed of two interlocked negative feedback loops: a per-tim loop, which is activated by dCLK-CYC and repressed by PER-TIM, and a dClk loop, which is repressed by dCLK-CYC and derepressed by PER-TIM.
authors.affiliation: Department of Biology and Biochemistry and Biological Clocks Program, University of Houston, Houston, TX 77204-5513, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Glossop
authors.forename: L C
authors.initials: LC
authors.lastname: Lyons
authors.forename: P E
authors.initials: PE
authors.lastname: Hardin
mesh_terms: D000818:Animals; D001683:Biological Clocks; D056926:CLOCK Proteins; D002940:Circadian Rhythm; D019281:Dimerization; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D005246:Feedback; D005786:Gene Expression Regulation; D017344:Genes, Insect; D019476:Insect Proteins / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C120526:Clk protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C096445:tim protein, Drosophila; D056926:CLOCK Proteins