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Doubletime (gene)
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Doubletime (gene)
Doubletime (DBT), also known as discs overgrown (DCO), is a gene that encodes the doubletime protein in fruit flies (Drosophila melanogaster). Michael Young and his team at Rockefeller University first identified and characterized the gene in 1998.
The DBT-encoded protein is a kinase that phosphorylates the period (PER) protein, which is crucial in controlling the biological clock that regulates circadian rhythms. Various mutations in the DBT gene have been observed to cause alterations in the period of locomotor activity in flies, including lengthening, shortening, or complete loss of the period in flies. In mammals, the homolog of DBT is casein kinase I epsilon, which has a similar role in regulating the circadian rhythm.
The circadian function of Drosophila and certain vertebrate Casein kinase 1 enzymes has been conserved over a long evolutionary timescale, making DBT and its homologs essential targets for research into the molecular mechanisms that underlie circadian rhythm regulation in various organisms.
The doubletime gene (DBT) was first discovered and characterized in 1998 by Michael Young and his team at Rockefeller University. Young's research group, headed by Jeffrey Price, published their findings in a paper which characterized three alleles of DBT in fruit flies. It was reported that two mutant alleles, named short and long (DBTs and DBTl, respectively), were able to disrupt the normal cycling of the genes Period (per) and Timeless (TIM).
The team suspected that the delay between the rise in mRNA levels of per and TIM and the rise of PER and TIM protein was 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 breakdown not possible. This work showed that DBT regulated the break-down of PER.
Young named the novel gene "doubletime" due to its effect on the normal period of Drosophila. Mutant flies that only expressed DBTS had an 18-hour period, while those expressing DBTL had a 28-hour period. Young's team also identified a third allele, DBTP, which is lethal to pupae while ablating any per or TIM products in larvae. DBTP mutants are important because they provided clues as to how the gene product functioned.
Without functional DBT protein, flies accumulate high levels of PER. These PER proteins do not disintegrate without pairing with TIM proteins. These mutants expressed higher cytosolic levels of PER than cells in which PER protein was associated with TIM protein. The doubletime gene regulates the expression of PER, which in turn controls circadian rhythm. Young's team later cloned the DBT gene and found that the DBT protein was a kinase that specifically phosphorylated PER proteins; they concluded that PER proteins were not phosphorylated by DBT protein in DBTP mutants.
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Doubletime (gene)
Doubletime (DBT), also known as discs overgrown (DCO), is a gene that encodes the doubletime protein in fruit flies (Drosophila melanogaster). Michael Young and his team at Rockefeller University first identified and characterized the gene in 1998.
The DBT-encoded protein is a kinase that phosphorylates the period (PER) protein, which is crucial in controlling the biological clock that regulates circadian rhythms. Various mutations in the DBT gene have been observed to cause alterations in the period of locomotor activity in flies, including lengthening, shortening, or complete loss of the period in flies. In mammals, the homolog of DBT is casein kinase I epsilon, which has a similar role in regulating the circadian rhythm.
The circadian function of Drosophila and certain vertebrate Casein kinase 1 enzymes has been conserved over a long evolutionary timescale, making DBT and its homologs essential targets for research into the molecular mechanisms that underlie circadian rhythm regulation in various organisms.
The doubletime gene (DBT) was first discovered and characterized in 1998 by Michael Young and his team at Rockefeller University. Young's research group, headed by Jeffrey Price, published their findings in a paper which characterized three alleles of DBT in fruit flies. It was reported that two mutant alleles, named short and long (DBTs and DBTl, respectively), were able to disrupt the normal cycling of the genes Period (per) and Timeless (TIM).
The team suspected that the delay between the rise in mRNA levels of per and TIM and the rise of PER and TIM protein was 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 breakdown not possible. This work showed that DBT regulated the break-down of PER.
Young named the novel gene "doubletime" due to its effect on the normal period of Drosophila. Mutant flies that only expressed DBTS had an 18-hour period, while those expressing DBTL had a 28-hour period. Young's team also identified a third allele, DBTP, which is lethal to pupae while ablating any per or TIM products in larvae. DBTP mutants are important because they provided clues as to how the gene product functioned.
Without functional DBT protein, flies accumulate high levels of PER. These PER proteins do not disintegrate without pairing with TIM proteins. These mutants expressed higher cytosolic levels of PER than cells in which PER protein was associated with TIM protein. The doubletime gene regulates the expression of PER, which in turn controls circadian rhythm. Young's team later cloned the DBT gene and found that the DBT protein was a kinase that specifically phosphorylated PER proteins; they concluded that PER proteins were not phosphorylated by DBT protein in DBTP mutants.