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PER1
The PER1 gene encodes the period circadian protein homolog 1 protein in humans. Function The PER1 protein is important to the maintenance of circadian rhythms in cells, and may also play a role in the development of cancer. This gene is a member of the period family of genes. It is expressed with a daily oscillating circadian rhythm, or an oscillation that cycles with a period of approximately 24 hours. PER1 is most notably expressed in the region of the brain called the suprachiasmatic nucleus (SCN), which is the primary circadian pacemaker in the mammalian brain. PER1 is also expressed throughout mammalian peripheral tissues. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression of PER1 in the suprachiasmatic nucleus will free-run in constant darkness, meaning that the 24-hour period of the cycle will persist without the aid of external light cues. Subsequently, a shift in the light/dark cycle evo ...
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PER3
The PER3 gene encodes the period circadian protein homolog 3 protein in humans. PER3 is a paralog to the PER1 and PER2 genes. It is a circadian gene associate with delayed sleep phase syndrome in humans. History The Per3 gene was independently cloned by two research groups (Kobe University School of Medicine and the Harvard Medical School) who both published their discovery in June 1998. The mammalian Per3 was discovered by searching for homologous cDNA sequences to Per2. The amino acid sequence of the mouse PERIOD3 protein (mPER3) is between 37-56% similar to the other two PER proteins. Function This gene is a member of the Period family of genes. It is expressed in a circadian pattern in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression in the SCN continues in constant darkness, and a shift in the ligh ...
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PER2
PER2 is a protein in mammals encoded by the ''PER2'' gene. ''PER2'' is noted for its major role in circadian rhythms. Discovery The ''per ''gene'' ''was first discovered using forward genetics in ''Drosophila melanogaster, Drosophilla melanogaster'' in 1971. Mammal, Mammalian Per2 was discovered by in 1997 through a search for homologous cDNA sequences to PER1. It is more similar to Drosophila ''Period (gene), per'' than its Sequence homology, paralogs. Later experiments in also identified ''Per2 ''in humans. Function ''PER2'' is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythm, circadian clock, which regulates the daily rhythms of locomotor activity, metabolism, and behavior. Circadian expression of these genes and their encoded proteins in the suprachiasmatic nucleus. Human PER2 is involved in h ...
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Period (gene)
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. Discovery 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 not 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 ...
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E-box
An E-box (enhancer box) is a DNA response element found in some eukaryotes that acts as a protein-binding site and has been found to regulate gene expression in neurons, muscles, and other tissues. Its specific DNA sequence, CANNTG (where N can be any nucleotide), with a palindromic canonical sequence of CACGTG, is recognized and bound by transcription factors to initiate gene transcription. Once the transcription factors bind to the promoters through the E-box, other enzymes can bind to the promoter and facilitate transcription from DNA to mRNA. Discovery The E-box was discovered in a collaboration between Susumu Tonegawa's and Walter Gilbert's laboratories in 1985 as a control element in immunoglobulin heavy-chain enhancer. They found that a region of 140 base pairs in the tissue-specific transcriptional enhancer element was sufficient for different levels of transcription enhancement in different tissues and sequences. They suggested that proteins made by specific tissues acted ...
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Circadian
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to the environment ( entrained by the environment). These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. The term ''circadian'' comes from the Latin ''circa'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cycles. In clinical settings, an abnormal circadian rhythm in humans ...
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Suprachiasmatic Nucleus
The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle. The mouse SCN contains approximately 20,000 neurons. The SCN interacts with many other regions of the brain. It contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters. Neuroanatomy The SCN is situated in the anterior part of the hypothalamus immediately dorsal, or ''superior'' (hence supra) to the optic chiasm (CHO) bilateral to (on either side of) the third ventricle. The nucleus can be divided into ventrolateral and dorsolateral portions, also known as the core and shell, respectively. These regions differ in their expression of the clock genes, the core expresses them in response to stimuli whereas ...
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Circadian Rhythm
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the environment (Entrainment (chronobiology), entrained by the environment). These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. The term ''circadian'' comes from the Latin ''wikt:circa#Latin, circa'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cy ...
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Suprachiasmatic Nucleus
The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle. The mouse SCN contains approximately 20,000 neurons. The SCN interacts with many other regions of the brain. It contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters. Neuroanatomy The SCN is situated in the anterior part of the hypothalamus immediately dorsal, or ''superior'' (hence supra) to the optic chiasm (CHO) bilateral to (on either side of) the third ventricle. The nucleus can be divided into ventrolateral and dorsolateral portions, also known as the core and shell, respectively. These regions differ in their expression of the clock genes, the core expresses them in response to stimuli whereas ...
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BMAL1
Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) or brain and muscle ARNT-Like 1 (BMAL1) is a protein that in humans is encoded by the gene on chromosome 11, region p15.3. It's also known as ''BMAL1'', ''MOP3'', and, less commonly, ''bHLHe5'', ''BMAL'', ''BMAL1C'', ''JAP3'', ''PASD3'', and ''TIC''. ''ARNTL'' encodes a transcription factor with a basic helix-loop-helix (bHLH) and two PAS domains. The human ''ARNTL'' gene has a predicted 24 exons, located on the p15 band of the 11th chromosome. The ARNTL protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. Research has revealed that ''ARNTL'' is the only clock gene without which the circadian clock fails to function in humans. ''ARNTL'' has also been identified as a candidate gene for susceptibility to hypertension, diabetes, ...
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CRY1
Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name ''cryptochrome'' was proposed as a ''portmanteau'' combining the '' chromatic'' nature of the photoreceptor, and the ''cryptogamic'' organisms on which many blue-light studies were carried out. The two genes ''Cry1'' and ''Cry2'' code the two cryptochrome proteins CRY1 and CRY2. In insects and plants, CRY1 regulates the circadian clock in a light-dependent fashion, whereas in mammals, CRY1 and CRY2 act as light-independent inhibitors of CLOCK-BMAL1 components of the circadian clock. In plants, blue-light photoreception can be used to cue developmental signals. Besides chlorophylls, cryptochromes are the only proteins known to form photoinduced radical-pairs ''in vivo''. These appear to enable some animal ...
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CRY2
Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name ''cryptochrome'' was proposed as a ''portmanteau'' combining the ''chromatic'' nature of the photoreceptor, and the ''cryptogamic'' organisms on which many blue-light studies were carried out. The two genes ''Cry1'' and ''Cry2'' code the two cryptochrome proteins CRY1 and CRY2. In insects and plants, CRY1 regulates the circadian clock in a light-dependent fashion, whereas in mammals, CRY1 and CRY2 act as light-independent inhibitors of CLOCK-BMAL1 components of the circadian clock. In plants, blue-light photoreception can be used to cue developmental signals. Besides chlorophylls, cryptochromes are the only proteins known to form photoinduced radical-pairs ''in vivo''. These appear to enable some animals ...
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Ataxia Telangiectasia Mutated
ATM serine/threonine kinase or Ataxia-telangiectasia mutated, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis. Several of these targets, including p53, CHK2, BRCA1, NBS1 and H2AX are tumor suppressors. In 1995, the gene was discovered by Yosef Shiloh who named its product ATM since he found that its mutations are responsible for the disorder ataxia–telangiectasia#Cause, ataxia–telangiectasia. In 1998, the Shiloh and Michael B. Kastan, Kastan laboratories independently showed that ATM is a protein kinase whose activity is enhanced by DNA damage. Introduction Throughout the cell cycle DNA is monitored for damage. Damages result from errors during DNA replication, replication, by-products of metabolism, general toxic drugs or ionizing radiation. The cell cycle has diffe ...
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