per

Summary

Gene Symbol: per
Description: period
Alias: CG2647, Clk, Dmel\CG2647, EG:155E2.4, PER, Per, clk-6, dPER, dmper, dper, mel_per, period, CG2647-PA, CG2647-PB, PERIOD, clock, clock-6, dperiod, per-PA, per-PB, period clock protein
Species: fruit fly
Products:     per

Top Publications

  1. Suri V, Hall J, Rosbash M. Two novel doubletime mutants alter circadian properties and eliminate the delay between RNA and protein in Drosophila. J Neurosci. 2000;20:7547-55 pubmed
    ..We have characterized two novel dbt mutants. Both cause a lengthening of behavioral period and profoundly alter period (per) and timeless (tim) transcript and protein profiles...
  2. Boothroyd C, Wijnen H, Naef F, Saez L, Young M. Integration of light and temperature in the regulation of circadian gene expression in Drosophila. PLoS Genet. 2007;3:e54 pubmed
    ..Transcripts encoding the clock components Period, Timeless, Clock, Vrille, PAR-domain protein 1, and Cryptochrome were all confirmed to be rhythmic after ..
  3. Zhang Y, Liu Y, Bilodeau Wentworth D, Hardin P, Emery P. Light and temperature control the contribution of specific DN1 neurons to Drosophila circadian behavior. Curr Biol. 2010;20:600-5 pubmed publisher
    ..Using a Clk-GAL4 driver that specifically targets a subset of DN1s, we generated mosaic per(0) flies with clock function restored only in these neurons. We found that the Clk4...
  4. Lim C, Allada R. ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila. Science. 2013;340:875-9 pubmed publisher
    ..protein involved in neurodegenerative disease, is a translational activator of the rate-limiting clock component PERIOD (PER) in Drosophila. ATX2 specifically interacted with TWENTY-FOUR (TYF), an activator of PER translation...
  5. Preuss F, Fan J, Kalive M, Bao S, Schuenemann E, Bjes E, et al. Drosophila doubletime mutations which either shorten or lengthen the period of circadian rhythms decrease the protein kinase activity of casein kinase I. Mol Cell Biol. 2004;24:886-98 pubmed
    In both mammals and fruit flies, casein kinase I has been shown to regulate the circadian phosphorylation of the period protein (PER)...
  6. Lim C, Lee J, Choi C, Kilman V, Kim J, Park S, et al. The novel gene twenty-four defines a critical translational step in the Drosophila clock. Nature. 2011;470:399-403 pubmed publisher
    ..Weak rhythms are accompanied by marked reductions in the levels of the clock protein Period (PER) as well as more modest effects on Timeless (TIM)...
  7. Beaver L, Rush B, Gvakharia B, Giebultowicz J. Noncircadian regulation and function of clock genes period and timeless in oogenesis of Drosophila melanogaster. J Biol Rhythms. 2003;18:463-72 pubmed
    ..Constitutive expression of the clock gene period was reported in the ovaries of Drosophila melanogaster; however, its molecular interactions and functional ..
  8. Stoleru D, Nawathean P, Fernández M, Menet J, Ceriani M, Rosbash M. The Drosophila circadian network is a seasonal timer. Cell. 2007;129:207-19 pubmed
    ..Together with the different entraining properties of the two clock centers, the results suggest that the functional organization of the network underlies the behavioral adjustment ..
  9. Yang M, Lee J, Padgett R, Edery I. Circadian regulation of a limited set of conserved microRNAs in Drosophila. BMC Genomics. 2008;9:83 pubmed publisher
    ..melanogaster miRNAs in adult heads of wildtype flies and the arrhythmic clock mutant cyc01...
  10. Zheng X, Koh K, Sowcik M, Smith C, Chen D, Wu M, et al. An isoform-specific mutant reveals a role of PDP1 epsilon in the circadian oscillator. J Neurosci. 2009;29:10920-7 pubmed publisher
    ..Importantly, the mutants show diminished expression of CLK and PERIOD (PER) in the central clock cells...

Detail Information

Publications108 found, 100 shown here

  1. Suri V, Hall J, Rosbash M. Two novel doubletime mutants alter circadian properties and eliminate the delay between RNA and protein in Drosophila. J Neurosci. 2000;20:7547-55 pubmed
    ..We have characterized two novel dbt mutants. Both cause a lengthening of behavioral period and profoundly alter period (per) and timeless (tim) transcript and protein profiles...
  2. Boothroyd C, Wijnen H, Naef F, Saez L, Young M. Integration of light and temperature in the regulation of circadian gene expression in Drosophila. PLoS Genet. 2007;3:e54 pubmed
    ..Transcripts encoding the clock components Period, Timeless, Clock, Vrille, PAR-domain protein 1, and Cryptochrome were all confirmed to be rhythmic after ..
  3. Zhang Y, Liu Y, Bilodeau Wentworth D, Hardin P, Emery P. Light and temperature control the contribution of specific DN1 neurons to Drosophila circadian behavior. Curr Biol. 2010;20:600-5 pubmed publisher
    ..Using a Clk-GAL4 driver that specifically targets a subset of DN1s, we generated mosaic per(0) flies with clock function restored only in these neurons. We found that the Clk4...
  4. Lim C, Allada R. ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila. Science. 2013;340:875-9 pubmed publisher
    ..protein involved in neurodegenerative disease, is a translational activator of the rate-limiting clock component PERIOD (PER) in Drosophila. ATX2 specifically interacted with TWENTY-FOUR (TYF), an activator of PER translation...
  5. Preuss F, Fan J, Kalive M, Bao S, Schuenemann E, Bjes E, et al. Drosophila doubletime mutations which either shorten or lengthen the period of circadian rhythms decrease the protein kinase activity of casein kinase I. Mol Cell Biol. 2004;24:886-98 pubmed
    In both mammals and fruit flies, casein kinase I has been shown to regulate the circadian phosphorylation of the period protein (PER)...
  6. Lim C, Lee J, Choi C, Kilman V, Kim J, Park S, et al. The novel gene twenty-four defines a critical translational step in the Drosophila clock. Nature. 2011;470:399-403 pubmed publisher
    ..Weak rhythms are accompanied by marked reductions in the levels of the clock protein Period (PER) as well as more modest effects on Timeless (TIM)...
  7. Beaver L, Rush B, Gvakharia B, Giebultowicz J. Noncircadian regulation and function of clock genes period and timeless in oogenesis of Drosophila melanogaster. J Biol Rhythms. 2003;18:463-72 pubmed
    ..Constitutive expression of the clock gene period was reported in the ovaries of Drosophila melanogaster; however, its molecular interactions and functional ..
  8. Stoleru D, Nawathean P, Fernández M, Menet J, Ceriani M, Rosbash M. The Drosophila circadian network is a seasonal timer. Cell. 2007;129:207-19 pubmed
    ..Together with the different entraining properties of the two clock centers, the results suggest that the functional organization of the network underlies the behavioral adjustment ..
  9. Yang M, Lee J, Padgett R, Edery I. Circadian regulation of a limited set of conserved microRNAs in Drosophila. BMC Genomics. 2008;9:83 pubmed publisher
    ..melanogaster miRNAs in adult heads of wildtype flies and the arrhythmic clock mutant cyc01...
  10. Zheng X, Koh K, Sowcik M, Smith C, Chen D, Wu M, et al. An isoform-specific mutant reveals a role of PDP1 epsilon in the circadian oscillator. J Neurosci. 2009;29:10920-7 pubmed publisher
    ..Importantly, the mutants show diminished expression of CLK and PERIOD (PER) in the central clock cells...
  11. Fujii S, Amrein H. Ventral lateral and DN1 clock neurons mediate distinct properties of male sex drive rhythm in Drosophila. Proc Natl Acad Sci U S A. 2010;107:10590-5 pubmed publisher
    ..Here, we genetically manipulate the molecular clock in different subsets of neurons and find that proper oscillation of the molecular clock in ventral lateral neurons ..
  12. Blanchardon E, Grima B, Klarsfeld A, Chelot E, Hardin P, Preat T, et al. Defining the role of Drosophila lateral neurons in the control of circadian rhythms in motor activity and eclosion by targeted genetic ablation and PERIOD protein overexpression. Eur J Neurosci. 2001;13:871-88 pubmed
    The ventral lateral neurons (LNvs) of the Drosophila brain that express the period (per) and pigment dispersing factor (pdf) genes play a major role in the control of circadian activity rhythms...
  13. Shafer O, Taghert P. RNA-interference knockdown of Drosophila pigment dispersing factor in neuronal subsets: the anatomical basis of a neuropeptide's circadian functions. PLoS ONE. 2009;4:e8298 pubmed publisher
    ..PDF's role in setting the period of free-running activity rhythms and the proper timing of evening activity under light:dark cycles emanates from ..
  14. Górska Andrzejak J, Makuch R, Stefan J, Görlich A, Semik D, Pyza E. Circadian expression of the presynaptic active zone protein Bruchpilot in the lamina of Drosophila melanogaster. Dev Neurobiol. 2013;73:14-26 pubmed publisher
    ..However, it also depends on the clock gene per, because it is abolished in the per(0) arrhythmic mutant...
  15. Darlington T, Lyons L, Hardin P, Kay S. The period E-box is sufficient to drive circadian oscillation of transcription in vivo. J Biol Rhythms. 2000;15:462-71 pubmed
    The minimum element from the Drosophila period promoter capable of driving in vivo cycling mRNA is the 69 bp circadian regulatory sequence (CRS)...
  16. Cyran S, Buchsbaum A, Reddy K, Lin M, Glossop N, Hardin P, et al. vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell. 2003;112:329-41 pubmed
    ..In one loop, dCLOCK/CYCLE activates period expression, and PERIOD protein then inhibits dCLOCK/CYCLE activity...
  17. Sehadova H, Glaser F, Gentile C, Simoni A, Giesecke A, Albert J, et al. Temperature entrainment of Drosophila's circadian clock involves the gene nocte and signaling from peripheral sensory tissues to the brain. Neuron. 2009;64:251-66 pubmed publisher
    ..Using luciferase imaging we demonstrate that brain clock neurons depend on signals from peripheral tissues in order to be synchronized by temperature...
  18. Gao F. Understanding fragile X syndrome: insights from retarded flies. Neuron. 2002;34:859-62 pubmed
    ..The relevance of these studies to our understanding of fragile X syndrome is discussed. ..
  19. Hendricks J, Lu S, Kume K, Yin J, Yang Z, Sehgal A. Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster. J Biol Rhythms. 2003;18:12-25 pubmed
    The central clock is generally thought to provide timing information for rest/activity but not to otherwise participate in regulation of these states...
  20. Lear B, Merrill C, Lin J, Schroeder A, Zhang L, Allada R. A G protein-coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior. Neuron. 2005;48:221-7 pubmed
    ..Disruption of the receptor is accompanied by phase-advanced oscillations of the core clock protein PERIOD. Moreover, effects on circadian timing induced by perturbation of PDF neurons require gop...
  21. Kim E, Edery I. Balance between DBT/CKIepsilon kinase and protein phosphatase activities regulate phosphorylation and stability of Drosophila CLOCK protein. Proc Natl Acad Sci U S A. 2006;103:6178-83 pubmed
    ..Drosophila, a homolog of vertebrate CKIepsilon, which regulates the progressive phosphorylation and stability of PERIOD (PER) proteins in animals...
  22. Fang Y, Sathyanarayanan S, Sehgal A. Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1). Genes Dev. 2007;21:1506-18 pubmed
    ..1 (PP1) in the regulation of the major timekeeping molecules in the Drosophila clock, TIMELESS (TIM) and PERIOD (PER)...
  23. Smith E, Lin J, Meissner R, Allada R. Dominant-negative CK2alpha induces potent effects on circadian rhythmicity. PLoS Genet. 2008;4:e12 pubmed publisher
    ..In Drosophila, circadian clocks consist of negative feedback loops in which the clock component PERIOD (PER) represses its own transcription...
  24. Martinek S, Young M. Specific genetic interference with behavioral rhythms in Drosophila by expression of inverted repeats. Genetics. 2000;156:1717-25 pubmed
    ..As an example, we show that inverted-repeat-mediated interference with the period gene produces a hypomorphic period phenotype...
  25. Kim E, Bae K, Ng F, Glossop N, Hardin P, Edery I. Drosophila CLOCK protein is under posttranscriptional control and influences light-induced activity. Neuron. 2002;34:69-81 pubmed
    In the Drosophila circadian clock, daily cycles in the RNA levels of dclock (dClk) are antiphase to those of period (per)...
  26. Ko H, Jiang J, Edery I. Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. Nature. 2002;420:673-8 pubmed
    ..A conserved feature of animal clocks is that Period (Per) proteins undergo daily rhythms in phosphorylation and levels, events that are crucial for normal clock ..
  27. Chang D, Reppert S. A novel C-terminal domain of drosophila PERIOD inhibits dCLOCK:CYCLE-mediated transcription. Curr Biol. 2003;13:758-62 pubmed
    The essence of the Drosophila circadian clock involves an autoregulatory feedback loop in which PERIOD (PER) and TIMELESS (TIM) inhibit their own transcription by association with the transcriptional activators dCLOCK (dCLK) and CYCLE (..
  28. Helfrich Forster C, Shafer O, Wülbeck C, Grieshaber E, Rieger D, Taghert P. Development and morphology of the clock-gene-expressing lateral neurons of Drosophila melanogaster. J Comp Neurol. 2007;500:47-70 pubmed
    The clock-gene-expressing lateral neurons are essential for the locomotor activity rhythm of Drosophila melanogaster...
  29. Glossop N, Hardin P. Central and peripheral circadian oscillator mechanisms in flies and mammals. J Cell Sci. 2002;115:3369-77 pubmed
    ..The core feedback loop in peripheral oscillators might therefore be functionally well conserved, and central oscillators could be specialized versions of a basic oscillator design. ..
  30. Li Q, Lang X. Internal noise-sustained circadian rhythms in a Drosophila model. Biophys J. 2008;94:1983-94 pubmed
    ..the deterministic model, the coherence of noisy circadian oscillations is suppressed by internal noise, while the period remains nearly constant over a large range of noise intensity, demonstrating robustness of the Drosophila model ..
  31. Matsumoto A, Ukai Tadenuma M, Yamada R, Houl J, Uno K, Kasukawa T, et al. A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes Dev. 2007;21:1687-700 pubmed
    The Drosophila circadian clock consists of integrated autoregulatory feedback loops, making the clock difficult to elucidate without comprehensively identifying the network components in vivo...
  32. Donlea J, Ramanan N, Shaw P. Use-dependent plasticity in clock neurons regulates sleep need in Drosophila. Science. 2009;324:105-8 pubmed publisher
    ..We found that flies mutant for rutabaga, period, and blistered were deficient for experience-dependent increases in sleep...
  33. Beaver L, Hooven L, Butcher S, Krishnan N, Sherman K, Chow E, et al. Circadian clock regulates response to pesticides in Drosophila via conserved Pdp1 pathway. Toxicol Sci. 2010;115:513-20 pubmed publisher
    ..clock consists of positive elements encoded by cycle (cyc) and Clock (Clk) and negative elements encoded by period (per) and timeless (tim) genes...
  34. Collins B, Rosato E, Kyriacou C. Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C. Proc Natl Acad Sci U S A. 2004;101:1945-50 pubmed
    ..activity responds to different seasonal conditions by thermosensitive regulation of splicing of a 3' intron in the period mRNA transcript...
  35. Kuo T, Pike D, Beizaeipour Z, Williams J. Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFkappaB Relish. BMC Neurosci. 2010;11:17 pubmed publisher
    ..Behavioral features of sleep as well as the innate immune response signaling pathways are well characterized in flies and are highly conserved in mammals...
  36. Chen C, Wu J, Lin H, Pai T, Fu T, Wu C, et al. Visualizing long-term memory formation in two neurons of the Drosophila brain. Science. 2012;335:678-85 pubmed publisher
    ..protein (CREB)-dependent transcriptional activation of calcium/calmodulin-dependent protein kinase II and period genes in the DAL neurons after spaced but not massed training...
  37. Bywalez W, Menegazzi P, Rieger D, Schmid B, Helfrich Forster C, Yoshii T. The dual-oscillator system of Drosophila melanogaster under natural-like temperature cycles. Chronobiol Int. 2012;29:395-407 pubmed publisher
    ..The bimodal activity rhythm was absent in the circadian clock mutants Clk(Jrk) and cyc(01) and reduced in per(01) and tim(01) mutants...
  38. Glaser F, Stanewsky R. Temperature synchronization of the Drosophila circadian clock. Curr Biol. 2005;15:1352-63 pubmed
    ..We show here that temperature cycles induce synchronized behavioral rhythms and oscillations of the clock proteins PERIOD and TIMELESS in constant light, a situation that normally leads to molecular and behavioral arrhythmicity...
  39. Akten B, Tangredi M, Jauch E, Roberts M, Ng F, Raabe T, et al. Ribosomal s6 kinase cooperates with casein kinase 2 to modulate the Drosophila circadian molecular oscillator. J Neurosci. 2009;29:466-75 pubmed publisher
    ..Importantly, an S6KII null mutant exhibits a short-period circadian phenotype that can be rescued by expression of the wild-type gene in clock neurons, indicating a role ..
  40. Xie Z, Kulasiri D, Samarasinghe S, Qian J. An unbiased sensitivity analysis reveals important parameters controlling periodicity of circadian clock. Biotechnol Bioeng. 2010;105:250-9 pubmed publisher
    ..approach to determine the relative importance of parameters controlling the performance of the circadian clock in Drosophila...
  41. Cusumano P, Klarsfeld A, Chélot E, Picot M, Richier B, Rouyer F. PDF-modulated visual inputs and cryptochrome define diurnal behavior in Drosophila. Nat Neurosci. 2009;12:1431-7 pubmed publisher
    ..The LN-EO thus integrates light inputs and PDF signaling to control Drosophila diurnal behavior, revealing a new clock-independent function for PDF.
  42. Rosato E, Codd V, Mazzotta G, Piccin A, Zordan M, Costa R, et al. Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY. Curr Biol. 2001;11:909-17 pubmed
    ..Although TIM dimerizes with PERIOD (PER), no association between CRY and PER has previously been revealed, and aspects of the light dependence of the ..
  43. Shahidullah M, Reddy S, Fei H, Levitan I. In vivo role of a potassium channel-binding protein in regulating neuronal excitability and behavior. J Neurosci. 2009;29:13328-37 pubmed publisher
    ..Together, these results indicate that Slob may serve a novel regulatory function in feeding behavior, possibly by influencing the excitability of the PI neurons...
  44. Szabó A, Papin C, Zorn D, Ponien P, Weber F, Raabe T, et al. The CK2 kinase stabilizes CLOCK and represses its activity in the Drosophila circadian oscillator. PLoS Biol. 2013;11:e1001645 pubmed publisher
    ..In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional activity...
  45. Chen K, Possidente B, Lomas D, Crowther D. The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer's disease. Dis Model Mech. 2014;7:445-58 pubmed publisher
    ..an age-related loss of circadian behavioural rhythms despite ongoing normal molecular oscillations in the central clock neurons...
  46. Panda S, Hogenesch J, Kay S. Circadian rhythms from flies to human. Nature. 2002;417:329-35 pubmed
    ..Although the existence of a circadian clock in humans had been postulated for decades, an understanding of the molecular mechanisms has required the full ..
  47. Ivanchenko M, Stanewsky R, Giebultowicz J. Circadian photoreception in Drosophila: functions of cryptochrome in peripheral and central clocks. J Biol Rhythms. 2001;16:205-15 pubmed
    ..In cry(b) flies, light applied during the dark period failed to induce degradation of TIM both in MTs and in LNs, yet attenuated cycling of TIM was observed in both ..
  48. Cyran S, Yiannoulos G, Buchsbaum A, Saez L, Young M, Blau J. The double-time protein kinase regulates the subcellular localization of the Drosophila clock protein period. J Neurosci. 2005;25:5430-7 pubmed
    The Period (PER), Timeless (TIM), and Double-Time (DBT) proteins are essential components of one feedback loop in the Drosophila circadian molecular clock. PER and TIM physically interact...
  49. Weber P, Kula Eversole E, Pyza E. Circadian control of dendrite morphology in the visual system of Drosophila melanogaster. PLoS ONE. 2009;4:e4290 pubmed publisher
    ..These were from confocal images of cross sections of L2 cells labeled with GFP. They were in wild-type and clock mutant flies held under different light conditions and sacrified at different time points...
  50. Zhang L, Lear B, Seluzicki A, Allada R. The CRYPTOCHROME photoreceptor gates PDF neuropeptide signaling to set circadian network hierarchy in Drosophila. Curr Biol. 2009;19:2050-5 pubmed publisher
    ..On the basis of our findings, we propose that CRY can gate PDF signaling to determine behavioral phase and network hierarchy. ..
  51. Ling J, Dubruille R, Emery P. KAYAK-? modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons. J Neurosci. 2012;32:16959-70 pubmed publisher
    ..In Drosophila, the dimeric transcription factor CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri), and PAR-domain protein 1 (Pdp1) transcription...
  52. Zhou X, Yuan C, Guo A. Drosophila olfactory response rhythms require clock genes but not pigment dispersing factor or lateral neurons. J Biol Rhythms. 2005;20:237-44 pubmed
    ..They were also independent of locomotor activity. The olfactory response rhythms were lost in period or timeless mutant flies (per0, tim0), indicating that clock genes control circadian rhythms of olfactory behavior...
  53. Vosshall L. Into the mind of a fly. Nature. 2007;450:193-7 pubmed
  54. Houl J, Ng F, Taylor P, Hardin P. CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos. BMC Neurosci. 2008;9:119 pubmed publisher
    ..of transcriptional feedback loops in which CLOCK-CYCLE (CLK-CYC) heterodimers activate their feedback regulators period (per) and timeless (tim) via E-box mediated transcription...
  55. Abruzzi K, Rodriguez J, Menet J, Desrochers J, Zadina A, Luo W, et al. Drosophila CLOCK target gene characterization: implications for circadian tissue-specific gene expression. Genes Dev. 2011;25:2374-86 pubmed publisher
    ..The CLK/CYC heterodimer is joined 4-6 h later by the transcriptional repressor PERIOD (PER), indicating that the majority of CLK targets are regulated similarly to core circadian genes...
  56. Lyons L, Darlington T, Hao H, Houl J, Kay S, Hardin P. Specific sequences outside the E-box are required for proper per expression and behavioral rescue. J Biol Rhythms. 2000;15:472-82 pubmed
    A 69 bp circadian regulatory sequence (CRS) upstream of the per gene is sufficient to drive circadian transcription, mediate proper spatial expression, and rescue behavioral rhythmicity in per01 flies...
  57. Shafer O, Helfrich Forster C, Renn S, Taghert P. Reevaluation of Drosophila melanogaster's neuronal circadian pacemakers reveals new neuronal classes. J Comp Neurol. 2006;498:180-93 pubmed
    In the brain of the fly Drosophila melanogaster, approximately 150 clock-neurons are organized to synchronize and maintain behavioral rhythms, but the physiological and neurochemical bases of their interactions are largely unknown...
  58. Sheeba V, Sharma V, Gu H, Chou Y, O Dowd D, Holmes T. Pigment dispersing factor-dependent and -independent circadian locomotor behavioral rhythms. J Neurosci. 2008;28:217-27 pubmed publisher
    ..causes initial behavioral arrhythmicity followed by gradual long-term emergence of two concurrent short- and long-period circadian behavioral activity bouts in approximately 60% of flies...
  59. Ueda H, Hagiwara M, Kitano H. Robust oscillations within the interlocked feedback model of Drosophila circadian rhythm. J Theor Biol. 2001;210:401-6 pubmed
    A mechanism for generating circadian rhythms has been of major interest in recent years. After the discovery of per and tim, a model with a simple feedback loop involving per and tim has been proposed...
  60. Williams J, Su H, Bernards A, Field J, Sehgal A. A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK. Science. 2001;293:2251-6 pubmed
    ..Mutant flies show normal oscillations of the clock genes period (per) and timeless (tim) and of their corresponding proteins, but altered oscillations and levels of a clock-..
  61. Levine J, Funes P, Dowse H, Hall J. Advanced analysis of a cryptochrome mutation's effects on the robustness and phase of molecular cycles in isolated peripheral tissues of Drosophila. BMC Neurosci. 2002;3:5 pubmed
    Previously, we reported effects of the cry(b) mutation on circadian rhythms in period and timeless gene expression within isolated peripheral Drosophila tissues...
  62. Nitabach M, Blau J, Holmes T. Electrical silencing of Drosophila pacemaker neurons stops the free-running circadian clock. Cell. 2002;109:485-95 pubmed
    ..Pacemaker electrical silencing also stops the free-running oscillation of PERIOD (PER) and TIMELESS (TIM) proteins that constitutes the core of the cell-autonomous molecular clock...
  63. Lin Y, Han M, Shimada B, Wang L, Gibler T, Amarakone A, et al. Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2002;99:9562-7 pubmed
    We measured daily gene expression in heads of control and period mutant Drosophila by using oligonucleotide microarrays...
  64. Busza A, Emery Le M, Rosbash M, Emery P. Roles of the two Drosophila CRYPTOCHROME structural domains in circadian photoreception. Science. 2004;304:1503-6 pubmed
    ..This contrasts with the function of Arabidopsis CRY domains and demonstrates that insect and plant cryptochromes use different mechanisms. ..
  65. Dean M, Ballard J. Linking phylogenetics with population genetics to reconstruct the geographic origin of a species. Mol Phylogenet Evol. 2004;32:998-1009 pubmed
    ..Here, we infer the geographic origin of Drosophila simulans using 2,014 bp of the period locus from 63 lines collected from 18 countries...
  66. Petri B, Stengl M. Phase response curves of a molecular model oscillator: implications for mutual coupling of paired oscillators. J Biol Rhythms. 2001;16:125-41 pubmed
    ..In Drosophila melanogaster, the PDH-immunoreactive (PDH-ir) lateral neurons, which also express the clock genes period and timeless, are assumed to be circadian pacemaker cells themselves...
  67. Smolen P, Baxter D, Byrne J. A reduced model clarifies the role of feedback loops and time delays in the Drosophila circadian oscillator. Biophys J. 2002;83:2349-59 pubmed
    ..A negative feedback loop is included, in which PER protein represses per transcription by binding the dCLOCK transcription factor...
  68. Dunlap J. Physiology. Running a clock requires quality time together. Science. 2006;311:184-6 pubmed
  69. Kim E, Ko H, Yu W, Hardin P, Edery I. A DOUBLETIME kinase binding domain on the Drosophila PERIOD protein is essential for its hyperphosphorylation, transcriptional repression, and circadian clock function. Mol Cell Biol. 2007;27:5014-28 pubmed
    A common feature of animal circadian clocks is the progressive phosphorylation of PERIOD (PER) proteins from hypo- to hyperphosphorylated species, events that are highly dependent on casein kinase 1 epsilon (termed DOUBLETIME [DBT] in ..
  70. Mizrak D, Ruben M, Myers G, Rhrissorrakrai K, Gunsalus K, Blau J. Electrical activity can impose time of day on the circadian transcriptome of pacemaker neurons. Curr Biol. 2012;22:1871-80 pubmed publisher
    ..Here we demonstrate the inverse relationship: there are broad transcriptional changes in Drosophila clock neurons (LN(v)s) in response to altered electrical activity, including a large set of circadian genes...
  71. Yang Z, Sehgal A. Role of molecular oscillations in generating behavioral rhythms in Drosophila. Neuron. 2001;29:453-67 pubmed
    ..In Drosophila, RNA and protein levels of the period and timeless genes oscillate and the proteins autoregulate their transcription...
  72. Wülbeck C, Szabo G, Shafer O, Helfrich Forster C, Stanewsky R. The novel Drosophila tim(blind) mutation affects behavioral rhythms but not periodic eclosion. Genetics. 2005;169:751-66 pubmed
    ..A newly induced long-period timeless mutant, tim(blind), encodes a constitutively hypophosphorylated TIM protein...
  73. Yoshii T, Fujii K, Tomioka K. Induction of Drosophila behavioral and molecular circadian rhythms by temperature steps in constant light. J Biol Rhythms. 2007;22:103-14 pubmed
    ..peak ca 24 h after the transition, and the peak recurred for several cycles, suggesting that the underlying clock is reset...
  74. Zhao J, Kilman V, Keegan K, Peng Y, Emery P, Rosbash M, et al. Drosophila clock can generate ectopic circadian clocks. Cell. 2003;113:755-66 pubmed
    ..The function of the transcriptional activator, Clock, is necessary in both Drosophila and mammals for the expression of many core clock components...
  75. Richier B, Michard Vanhée C, Lamouroux A, Papin C, Rouyer F. The clockwork orange Drosophila protein functions as both an activator and a repressor of clock gene expression. J Biol Rhythms. 2008;23:103-16 pubmed publisher
    ..and CYCLE (CYC) basic helix-loop-helix (bHLH) PAS-domain transcription factors activate the expression of the period (per) and timeless (tim) genes...
  76. Currie J, Goda T, Wijnen H. Selective entrainment of the Drosophila circadian clock to daily gradients in environmental temperature. BMC Biol. 2009;7:49 pubmed publisher
    ..The temperature-entrained phase relationship between clock gene expression rhythms and locomotor activity rhythms strongly resembled that previously observed for light ..
  77. Zhang Y, Ling J, Yuan C, Dubruille R, Emery P. A role for Drosophila ATX2 in activation of PER translation and circadian behavior. Science. 2013;340:879-82 pubmed publisher
    A negative transcriptional feedback loop generates circadian rhythms in Drosophila. PERIOD (PER) is a critical state-variable in this mechanism, and its abundance is tightly regulated...
  78. Martinek S, Inonog S, Manoukian A, Young M. A role for the segment polarity gene shaggy/GSK-3 in the Drosophila circadian clock. Cell. 2001;105:769-79 pubmed
    Tissue-specific overexpression of the glycogen synthase kinase-3 (GSK-3) ortholog shaggy (sgg) shortens the period of the Drosophila circadian locomotor activity cycle...
  79. Benito J, Houl J, ROMAN G, Hardin P. The blue-light photoreceptor CRYPTOCHROME is expressed in a subset of circadian oscillator neurons in the Drosophila CNS. J Biol Rhythms. 2008;23:296-307 pubmed publisher
    ..Given the importance of CRY to circadian clock function, we expected this protein to be expressed in all oscillator cells, yet CRY cellular distribution and ..
  80. Peschel N, Veleri S, Stanewsky R. Veela defines a molecular link between Cryptochrome and Timeless in the light-input pathway to Drosophila's circadian clock. Proc Natl Acad Sci U S A. 2006;103:17313-8 pubmed
    ..In Drosophila melanogaster, the circadian clock is synchronized with the natural environment by light-dependent degradation of the clock protein Timeless, ..
  81. Sekine T, Yamaguchi T, Hamano K, Young M, Shimoda M, Saez L. Casein kinase I epsilon does not rescue double-time function in Drosophila despite evolutionarily conserved roles in the circadian clock. J Biol Rhythms. 2008;23:3-15 pubmed publisher
    ..dbt and its mammalian ortholog casein kinase I epsilon (hckI epsilon) regulate the circadian phosphorylation of period (per), thus controlling per subcellular localization and stability...
  82. Hughes M, Grant G, Paquin C, Qian J, Nitabach M. Deep sequencing the circadian and diurnal transcriptome of Drosophila brain. Genome Res. 2012;22:1266-81 pubmed publisher
    ..sequencing (RNA-seq) to profile the circadian transcriptome of Drosophila melanogaster brain from wild-type and period-null clock-defective animals...
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    ..show different temporal patterns of circadian locomotor activity that are determined by the circadian clock gene period (per)...
  84. Hardin P. The circadian timekeeping system of Drosophila. Curr Biol. 2005;15:R714-22 pubmed
    ..I will also discuss where work remains to be done to give a comprehensive picture of the circadian clock in Drosophila and likely many other organisms.
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    ..Rhythms in H3-K9 acetylation and H3-K4 trimethylation are also associated with CLOCK-BMAL1-dependent transcription in mammals, indicating that the mechanism that controls rhythmic transcription is a ..
  86. Roenneberg T, Merrow M. The network of time: understanding the molecular circadian system. Curr Biol. 2003;13:R198-207 pubmed
    The circadian clock provides a temporal structure that modulates biological functions from the level of gene expression to performance and behaviour...
  87. Wijnen H, Naef F, Young M. Molecular and statistical tools for circadian transcript profiling. Methods Enzymol. 2005;393:341-65 pubmed
    ..Both comparative and temporal study designs are discussed, and their use in circadian research is illustrated with examples. Data analysis methods to assess periodic components in time series data are outlined in detail. ..
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    ..Under constant conditions of illumination and temperature, these internal biological rhythms persist with a period close to 1 day ("circadian"), but it is usually not exactly 24h...
  89. Lin Y, Stormo G, Taghert P. The neuropeptide pigment-dispersing factor coordinates pacemaker interactions in the Drosophila circadian system. J Neurosci. 2004;24:7951-7 pubmed
    ..To understand how PDF exerts its influence, we performed time-series immunostainings for the PERIOD protein in normal and pdf mutant flies over 9 d of constant conditions...
  90. Lim C, Chung B, Pitman J, McGill J, Pradhan S, Lee J, et al. Clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. Curr Biol. 2007;17:1082-9 pubmed
    ..transcription-factor heterodimer, CLOCK/CYCLE (CLK/CYC), transcriptionally activates the clock components period (per), timeless (tim), Par domain protein 1 (Pdp1), and vrille (vri), which feed back and regulate distinct ..
  91. Menet J, Abruzzi K, Desrochers J, Rodriguez J, Rosbash M. Dynamic PER repression mechanisms in the Drosophila circadian clock: from on-DNA to off-DNA. Genes Dev. 2010;24:358-67 pubmed publisher
    ..We report here in the Drosophila model two different mechanisms by which the circadian repressor PERIOD (PER) inhibits CLOCK/CYCLE (CLK/CYC)-mediated transcription...
  92. Gentile C, Sehadova H, Simoni A, Chen C, Stanewsky R. Cryptochrome antagonizes synchronization of Drosophila's circadian clock to temperature cycles. Curr Biol. 2013;23:185-95 pubmed publisher
    ..Using spatially restricted expression of the clock gene period, we show that dorsally located clock neurons mainly mediate synchronization to higher (20°C:29°C) and ventral ..
  93. Collins B, Mazzoni E, Stanewsky R, Blau J. Drosophila CRYPTOCHROME is a circadian transcriptional repressor. Curr Biol. 2006;16:441-9 pubmed
    Although most circadian clock components are conserved between Drosophila and mammals, the roles assigned to the CRYPTOCHROME (CRY) proteins are very different: Drosophila CRY functions as a circadian photoreceptor, whereas mammalian CRY ..
  94. Busza A, Murad A, Emery P. Interactions between circadian neurons control temperature synchronization of Drosophila behavior. J Neurosci. 2007;27:10722-33 pubmed
    ..In conclusion, the behavioral responses to temperature input are determined by both the individual properties of specific groups of circadian neurons and their organization in a neural network. ..
  95. Krishnan N, Kretzschmar D, Rakshit K, Chow E, Giebultowicz J. The circadian clock gene period extends healthspan in aging Drosophila melanogaster. Aging (Albany NY). 2009;1:937-48 pubmed
    ..We examined effects of a null mutation in the circadian clock gene period (per(01)) on the fly healthspan by challenging aging flies with short-term oxidative stress (24h hyperoxia) and ..
  96. Kula Eversole E, Nagoshi E, Shang Y, Rodriguez J, Allada R, Rosbash M. Surprising gene expression patterns within and between PDF-containing circadian neurons in Drosophila. Proc Natl Acad Sci U S A. 2010;107:13497-502 pubmed publisher
    ..Although half of the l-LNv-enriched mRNA population, including core clock mRNAs, is shared between the l-LNvs and s-LNvs, the other half is l-LNv- and s-LNv-specific...
  97. Vodovar N, Clayton J, Costa R, Odell M, Kyriacou C. The Drosophila clock protein Timeless is a member of the Arm/HEAT family. Curr Biol. 2002;12:R610-1 pubmed
  98. Hara T, Koh K, Combs D, Sehgal A. Post-translational regulation and nuclear entry of TIMELESS and PERIOD are affected in new timeless mutant. J Neurosci. 2011;31:9982-90 pubmed publisher
    ..In Drosophila melanogaster, the idea that nuclear entry of PERIOD (PER) is controlled by its partner protein TIMELESS (TIM) has been challenged by several studies...
  99. Vanin S, Bhutani S, Montelli S, Menegazzi P, Green E, Pegoraro M, et al. Unexpected features of Drosophila circadian behavioural rhythms under natural conditions. Nature. 2012;484:371-5 pubmed publisher
    ..rhythmic locomotor behaviour provides the main phenotype for the identification of higher eukaryotic clock genes...
  100. Giebultowicz J. Peripheral clocks and their role in circadian timing: insights from insects. Philos Trans R Soc Lond B Biol Sci. 2001;356:1791-9 pubmed
    ..animal, such as an insect, and what are their roles and the relationships between them? Most attempts to locate clock-containing tissues were based on the analysis of behavioural rhythms and identified brain-located timing centres ..