High impact information on per

• We propose that Clock is uniquely able to induce and organize the core elements of interdependent feedback loops necessary for circadian rhythms [1].
• We demonstrate in Drosophila that Clock misexpression in nai;ve brain regions induces circadian gene expression [1].
• Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime [2].
• 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 progression [2].
• Here we present the crystal structure of a Drosophila PERIOD (dPER) fragment comprising two tandemly organized PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B) and two additional C-terminal alpha helices (alphaE and alphaF) [3].

Biological context of per

• Circadian rhythms are controlled by the periodic accumulation of Period proteins, which act as transcriptional repressors of Clock-dependent genes [4].
• Clk was previously mapped, by meiotic recombination, very close to the period(per) locus on the X chromosome [5].
• The Clk(ar) phenotype is caused by a splice site mutation that severely disrupts splicing and reduces Clk activity [6].

Associations of per with chemical compounds

• Cocaine-induced sensitization is reportedly impaired in Drosophila melanogaster mutant for the Period (Per) gene [7].
• Clinal variation for repeat number in the Thr-Gly region of the period circadian timing gene in Drosophila melanogaster was described in Europe and has subsequently been used as evidence of thermal selection on period alleles [8].

Other interactions of per

• Consistent with a direct action on the clock mechanism, we show that CK2beta is localized within clock neurons and that the clock proteins Period (Per) and Timeless (Tim) accumulate to abnormally high levels in the Andante mutant [9].
• We cloned Clock, Bmal, and Timeless homologs (apClock, apBmal, and apTimeless) from the silkmoth Antheraea pernyi, from which a Period homolog (apPeriod) has already been cloned [10].
• The Drosophila PERIOD (dPER) protein is phosphorylated by the serine?threonine protein kinase, DOUBLETIME (DBT) [11].
• Two basic helix-loop-helix (bHLH) PAS (PER-ARNT-SIM) transcription factors, CLOCK and BMAL1, form the positive elements of the system and drive transcription of three Period and two Cryptochrome genes [12].
• We propose that dCREB2 supports cycling of the Period/Timeless oscillator [13].

Analytical, diagnostic and therapeutic context of per

• As an initial step to understand the molecular mechanism of mammalian circadian clock, we screened His-tagged dPER/PAS binding proteins from rat brain nuclear extracts, using Ni2+-NTA affinity chromatography [14].
• Analysis of period circadian expression in the Drosophila head by in situ hybridization [15].

References