Doubletime (gene)
| doubletime | |
|---|---|
| Identifiers | |
| Organism | |
| Symbol | dbt |
| Alt. symbols | dco |
| Entrez | 43673 |
| RefSeq (mRNA) | NM_001276203.1 |
| RefSeq (Prot) | NP_001263132.1 |
| UniProt | O76324 |
| Other data | |
| EC number | 2.7.11.1 |
| Chromosome | 3R: 26.88 - 26.89 Mb |
| casein kinase 1, epsilon | |
|---|---|
| Identifiers | |
| Symbol | CSNK1E |
| Entrez | 1454 |
| HUGO | 2453 |
| OMIM | 121695 |
| RefSeq | NM_001894 |
| UniProt | P49674 |
| Other data | |
| EC number | 2.7.11.1 |
| Locus | Chr. 22 q13.1 |
Doubletime (dbt) also known as discs overgrown (dco) is a gene that encodes the double-time protein (DBT) in Drosophila melanogaster. The double-time protein is a kinase that phosphorylates PER protein that regulates the molecularly-driven, biological clock controlling circadian rhythm. The mammalian homolog of doubletime is casein kinase I, epsilon. Different Mutations in the dbt gene have been shown to cause lengthening, shortening, or complete loss in period of locomotor activity in flies. Drosophila and certain vertebrate Casein Kinase Id shows circadian function that has been evolutionary conserved over long time spans.
Double time gene (dbt) was first identified and characterized in 1998 by Michael Young and his team at The Rockefeller University. Young’s research group, headed by Jeffrey Price, published their results in a paper which characterized three alleles of dbt in fruit flies. They discovered that two mutant alleles, named short and long (dbts and dbtl, respectively) that were able to alter normal cycling of per and tim. Young’s team suspected that the delay between the rise in mRNA levels of per and tim and the rise of PER and TIM protein were due to the effects of another protein. Young suspected that this protein postponed the intercellular accumulation of PER protein by destroying it. Only when PER was paired with TIM was this break-down not possible. This work showed that DBT regulated the break-down of PER.
Young named the novel gene double-time (dbt) due to its effect on the normal period of Drosophila. Mutant flies which only expressed dbts had an 18-hour period while those expressing dbtl had a 28-hour period. In addition, Young’s team isolated a third allele, dbtp' which caused lethality in pupa while ablating any per or tim products in larvae.dbtp mutants were important because they provided clues as to how the gene product functioned. Without functional DBT protein, flies accumulated high levels of PER and these PER proteins do not disintegrate in the absence of pairing with TIM protein. These mutants expressed higher cytosolic levels of PER than cells in which PER protein was associated with TIM protein. The double-time gene regulates the expression of PER which in turns controls circadian rhythm. Young’s team later cloned the dbt gene and found that the DBT protein was a kinase which specifically phosphorylated PER proteins. Thus, in dbt mutants, PER proteins were not phosphorylated by DBT protein.
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