Cycle (gene)

Cycle
The approximate 3D structure of CYC protein generated with Phyre2. The protein sequence information was obtained from the UniProt database.
Identifiers
Organism	Drosophila melanogaster
Symbol	cyc
Entrez	40162
RefSeq (mRNA)	NM_079444.3
RefSeq (Prot)	NP_524168.2
UniProt	O61734
Other data
Chromosome	3L: 19.81 - 19.81 Mb

Cycle (cyc) is a gene in Drosophila melanogaster that encodes the CYCLE protein (CYC). The Cycle gene (cyc) is expressed in a variety of cell types in a circadian manner. It is involved in controlling both the sleep-wake cycle and circadian regulation of gene expression by promoting transcription in a negative feedback mechanism. The cyc gene is located on the left arm of chromosome 3 and codes for a transcription factor containing a basic helix-loop-helix (bHLH) domain and a PAS domain. The 2.17 kb cyc gene is divided into 5 coding exons totaling 1,625 base pairs which code for 413 aminos acid residues. Currently 19 alleles are known for cyc .Orthologs performing the same function in other species include ARNTL and BMAL1.

Cycle is primarily known for its role in the genetic transcription-translation feedback loop that generates circadian rhythms in Drosophila. In the cell nucleus, the CYCLE protein (CYC) forms a heterodimer with a second bHLH-PAS protein, CLOCK (CLK). This CYC-CLK protein complex binds to E-box elements in promoter regions of the genes period and timeless, functioning as a transcription factor in the translation of the proteins PER and TIM. After the PER and TIM proteins accumulate in the cytoplasm and bind together, the PER-TIM complex translocates to the nucleus. The TIM protein in these complexes mediate the accumulation of the dimeric PER-TIM protein complex and their subsequent importation into the nucleus, where the PER protein in these complexes then mediates the release of CYC-CLK from the chromatin, repressing CYC-CLK dependent transcription. Thus, CLK and CYC act as positive factors and PER and TIM as negative factors. CYC also plays a role in the post-translational regulation of CLK in the cytoplasm. These four proteins of the feedback loop are later degraded by a casein kinase-mediated phosphorylation cycle, allowing fluctuations in gene expression according to environmental cues. This cycle is called the transcription-translation feedback loop as demonstrated in this video by the Howard Hughes Medical Institution. Though cyc is a clock gene and plays a role in setting and keeping rhythms, cyc is expressed constitutively (continuously) in Drosophila cells and is present in native Drosophila tissue culture cells, unlike clk, per, or tim. Regulation thus occurs primarily through the negative feedback by the PER-TIM protein complex in the transcription-translation feedback loop described above.