Period (gene)
| period serina | |
|---|---|
| Identifiers | |
| Organism | |
| Symbol | per |
| Entrez | 31251 |
| RefSeq (mRNA) | NM_080317 |
| RefSeq (Prot) | NP_525056 |
| UniProt | P07663 |
| Other data | |
| Chromosome | X: 2.58 - 2.59 Mb |
| period homolog 1 (Drosophila) | |
|---|---|
| Identifiers | |
| Symbol | PER1 |
| Entrez | 5187 |
| HUGO | 8845 |
| OMIM | 602260 |
| RefSeq | NM_002616 |
| UniProt | O15534 |
| Other data | |
| Locus | Chr. 17 p12 |
| period homolog 2 (Drosophila) | |
|---|---|
| Identifiers | |
| Symbol | PER2 |
| Entrez | 8864 |
| HUGO | 8846 |
| OMIM | 603426 |
| RefSeq | NM_003894 |
| UniProt | O15055 |
| Other data | |
| Locus | Chr. 2 q37.3 |
| period homolog 3 (Drosophila) | |
|---|---|
| Identifiers | |
| Symbol | PER3 |
| Entrez | 8863 |
| HUGO | 8847 |
| OMIM | 603427 |
| RefSeq | NM_016831 |
| UniProt | P56645 |
| Other data | |
| Locus | Chr. 1 p36.23 |
Period (per) is a gene located on the X chromosome of Drosophila melanogaster. Oscillations in levels of both per transcript and its corresponding protein PER have a period of approximately 24 hours and together play a central role in the molecular mechanism of the Drosophila biological clock driving circadian rhythms in eclosion and locomotor activity. Mutations in the per gene can shorten (perS), lengthen (perL), and even abolish (per0) the period of the circadian rhythm.
The period gene and three mutants (perS, perL, and per0) were isolated in an EMS mutagenesis screen by Ronald Konopka and Seymour Benzer in 1971. The perS, perL, and per0 mutations were found to complement each other, so it was concluded that the three phenotypes were due to mutations in the same gene. The discovery of mutants that altered the period of circadian rhythms in eclosion and locomotor activity (perS and perL) indicated the role of the per gene in the clock itself and not an output pathway. The period gene was first sequenced in 1984 by Michael Rosbash and colleagues. In 1998, it was discovered that per produces two transcripts (differing only by the alternative splicing of a single untranslated intron) which both encode the PER protein.
In Drosophila, per mRNA levels oscillate with a period of approximately 24 hours, peaking during the early subjective night. The per product PER also oscillates with a nearly 24-hour period, peaking about six hours after per mRNA levels during the middle subjective night. When PER levels increase, the inhibition of per transcription increases, lowering the protein levels. However, because PER protein cannot directly bind to DNA, it does not directly influence its own transcription; alternatively, it inhibits its own activators. After PER is produced from per mRNA, it dimerizes with Timeless (TIM) and the complex goes into the nucleus and inhibits the transcription factors of per and tim, the CLOCK/CYCLE heterodimer. This CLOCK/CYCLE complex acts as a transcriptional activator for per and tim by binding to specific enhancers (called E-boxes) of their promoters. Therefore, inhibition of CLK/CYC lowers per and tim mRNA levels, which in turn lower the levels of PER and TIM. Now, cryptochrome (CRY) is a light sensitive protein which inhibits TIM in the presence of light. When TIM is not complexed with PER, another protein, doubletime, or DBT, phosphorylates PER, targeting it for degradation.
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