A backronym is an acronym formed from an already existing word by expanding its letters into the words of a phrase. Backronyms may be invented with either serious or humorous intent, or they may be a type of false etymology or folk etymology . The word is a portmanteau of back and acronym .
90-411: 4H10 9575 12753 ENSG00000134852 ENSMUSG00000029238 O15516 O08785 NM_001267843 NM_004898 NM_007715 NM_001289826 NM_001305222 NP_001254772 NP_004889 NP_001276755 NP_001292151 NP_031741 CLOCK ( backronym for circadian locomotor output cycles kaput ) is a gene encoding a basic helix-loop-helix - PAS transcription factor that
180-527: A 2021 study, metabolic outputs , measured by bowel movements , were severely different for participants who were wild type in comparison to those with the CRY1Δ11 variant. The participants with the variant had a delayed sleep cycle and delayed metabolic output when compared to the wild type. Magnetoreception is a sense which allows an organism to detect a magnetic field to perceive direction, altitude or location. Experimental data suggests that cryptochromes in
270-459: A backronym is "an acronym deliberately formed from a phrase whose initial letters spell out a particular word or words, either to create a memorable name or as a fanciful explanation of a word's origin". Many fictional espionage organizations are backronyms, such as SPECTRE (special executive for counterintelligence, terrorism, revenge and extortion) from the James Bond franchise. For example,
360-527: A central role as a transcription factor in the circadian pacemaker. In Drosophila , newly synthesized CLOCK (CLK) is hypophosphorylated in the cytoplasm before entering the nucleus. Once in the nuclei, CLK is localized in nuclear foci and is later redistributed homogeneously. CYCLE (CYC) (also known as dBMAL for the BMAL1 ortholog in mammals) dimerizes with CLK via their respective PAS domains . This dimer then recruits co-activator CREB-binding protein (CBP) and
450-438: A circadian role upstream of other clock genes and components. In mammals, cryptochrome proteins are encoded by two genes, Cry1 and Cry2. Cryptochrome is one of the four groups of mammalian clock genes/proteins that generate a transcription-translation negative-feedback loop (TTFL), along with Period (PER) , CLOCK , and BMAL1 . In this loop, CLOCK and BMAL1 proteins are transcriptional activators , which together bind to
540-495: A conserved domain with deoxyribodipyrimidine photolyase , and positions 288 through 486 show a conserved domain with the FAD binding domain of DNA photolyase. Comparative genomic analysis supports photolyase proteins as the ancestors of cryptochromes. However, by 1995 it became clear that the products of the HY4 gene and its two human homologs did not exhibit photolyase activity and were instead
630-548: A few primary leaves with a flower. A double loss-of-function mutation in Arabidopsis thaliana Early Flowering 3 (elf3) and Cry2 genes delays flowering under continuous light and was shown to accelerate it during long and short days, which suggests that Arabidopsis CRY2 may play a role in accelerating flowering time during continuous light. Cryptochromes receptors cause plants to respond to blue light via photomorphogenesis . They help control seed and seedling development, as well as
720-464: A ground state of FAD •. Researchers have also recently proposed a model in which FAD is excited to its doublet or quartet state by absorption of a photon, which then leads to a conformational change in the CRY protein. Also the ring eyes of the demosponge larva of Amphimedon queenslandica express a blue-light-sensitive cryptochrome (Aq-Cry2), which might mediate phototaxis. In contrast,
810-403: A light response in opsin -knockout Drosophila . Cryptochrome, like many genes involved in circadian rhythm, shows circadian cycling in mRNA and protein levels. In Drosophila , Cry mRNA concentrations cycle under a light-dark cycle (LD), with high levels in light and low levels in the dark. This cycling persists in constant darkness (DD), but with decreased amplitude. The transcription of
900-625: A light source, in response to blue light. This response is now known to have its own set of photoreceptors, the phototropins . Unlike phytochromes and phototropins, cryptochromes are not kinases . Their flavin chromophore is reduced by light and transported into the cell nucleus , where it affects the turgor pressure and causes subsequent stem elongation. To be specific, Cry2 is responsible for blue-light-mediated cotyledon and leaf expansion. Cry2 overexpression in transgenic plants increases blue-light-stimulated cotyledon expansion, which results in many broad leaves and no flowers rather than
990-431: A mediator of light sensitivity, significantly drops. In recent years, data have supported melanopsin as the main circadian photoreceptor, in particular melanopsin cells that mediate entrainment and communication between the eye and the suprachiasmatic nucleus (SCN). One of the main difficulties in confirming or denying CRY as a mammalian photoreceptor is that when the gene is knocked out the animal goes arrhythmic, so it
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#17328509731811080-401: A model by which energy captured by pterin is transferred to flavin. Under this model of phototransduction, FAD would then be reduced to FADH, which probably mediates the phosphorylation of a certain domain in cryptochrome. This could then trigger a signal transduction chain, possibly affecting gene regulation in the cell nucleus . A new hypothesis proposes that partner molecules sense
1170-429: A model in which the flavin cofactor exists in anion radical form, FAD •. Recently, researchers have observed that oxidized FAD is readily reduced to FAD • by light. Furthermore, mutations that blocked photoreduction had no effect on light-induced degradation of CRY, while mutations that altered the stability of FAD • destroyed CRY photoreceptor function. These observations provide support for
1260-541: A new class of blue light photoreceptor hypothesized to be circadian photopigments . In 1996 and 1998, Cry homologs were identified in Drosophila and mice , respectively. Cryptochromes (CRY1, CRY2) are evolutionarily old and highly conserved proteins that belong to the flavoproteins superfamily that exists in all kingdoms of life. Cryptochromes are derived from and closely related to photolyases, which are bacterial enzymes that are activated by light and involved in
1350-443: A pair of radicals with correlated spins when exposed to blue light. Radical pairs can also be generated by the light-independent dark reoxidation of the flavin cofactor by molecular oxygen through the formation of a spin-correlated FADH-superoxide radical pairs. Magnetoreception is hypothesized to function through the surrounding magnetic field's effect on the correlation (parallel or anti-parallel) of these radicals, which affects
1440-423: A photoreceptive role, as well as acting as negative regulators of Per gene expression in mice. In Drosophila , cryptochrome is only encoded by one Cry gene (d Cry) and functions as a blue light photoreceptor. Exposure to blue light induces a conformation similar to that of the always-active CRY mutant with a C-terminal deletion (CRYΔ). The half-life of this conformation is 15 minutes in the dark and facilitates
1530-490: A positive limb of a feedback loop. The binding of CLOCK-BMAL to an E-box promoter element activates transcription of clock genes such as per 1, 2, and 3 and tim in mice. It has been shown in mice that CLOCK-BMAL also activates the Nicotinamide phosphoribosyltransferase gene (also called Nampt ), part of a separate feedback loop. This feedback loop creates a metabolic oscillator. The CLOCK-BMAL dimer activates transcription of
1620-403: A role in nonparametric entrainment (entrainment by short discrete light pulses). However, the lateral neurons receive light information through both the blue light CRY pathway and the rhodopsin pathway. Therefore, CRY is involved in light perception and is an input to the circadian clock, however it is not the only input for light information, as a sustained rhythm has been shown in the absence of
1710-474: A scored questionnaire. This region is well conserved between mice and humans and polymorphisms have been shown to affect mRNA stability, indicating allelic variants could disrupt normal circadian patterns in mammals leading to conditions such as insomnia or other sleep disorders. Clock mutant organisms can either possess a null mutation or an antimorphic allele at the Clock locus that codes for an antagonist to
1800-502: A self-sustaining clock via gene duplication and functional divergence of clock genes. The kaiA / B / C gene clusters remain the oldest of the clock genes as they are present in cyanobacteria , with kai C most likely the ancestor of kai A and kaiB. The function of these ancestral clock genes was most likely related to chromosome function before evolving a timing mechanism. The kai A and kai B genes arose after cyanobacteria separated from other prokaryotes. Harsh climate conditions in
1890-528: Is a basic leucine zipper (bZIP) factor that promotes photomorphogenesis by binding to light-responsive genes. CRY interacts with G protein β-subunit AGB1, where HY5 dissociates from AGB1 and becomes activated. CRY interacts with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and PIF5, repressors of photomorphogenesis and promoter of hypocotyl elongation, to repress PIF4 and PIF5 transcription activity. Lastly, CRY can inhibit auxin and brassinosterioid (BR) signaling to promote photomorphogenesis. Despite much research on
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#17328509731811980-427: Is a circadian photoreceptor whereas CRY2 is a clock repressor which represses Clock/Cycle (Bmal1) complex in insects and vertebrates . 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 to detect magnetic fields. Cryptochromes have been
2070-467: Is delayed by approximately four hours relative to Cry1 promoter activation. This delay is independent of CRY1 or CRY2 levels and is mediated by a combination of E/E'-box and D-box elements in the promoter and RevErbA / ROR binding elements (RREs) in the gene's first intron. Transfection of arrhythmic Cry1 Cry2 double-knockout cells with only the Cry1 promoter (causing constitutive Cry1 expression)
2160-549: Is further phosphorylated. Once phosphorylated, this CLK-CYC complex binds to the E-box elements of the promoters of period (per) and timeless (tim) via its bHLH domain, causing the stimulation of gene expression of per and tim . A large molar excess of period (PER) and timeless (TIM) proteins causes formation of the PER-TIM heterodimer which prevents the CLK-CYC heterodimer from binding to
2250-460: Is hard to measure its capacity as purely a photoreceptor. However, some recent studies indicate that human CRY1 may mediate light response in peripheral tissues. Normal mammalian circadian rhythm relies critically on delayed expression of Cry1 following activation of the Cry1 promoter. Whereas rhythms in Per2 promoter activation and Per2 mRNA levels have almost the same phase, Cry1 mRNA production
2340-596: Is known to affect both the persistence and period of circadian rhythms . Research shows that the CLOCK gene plays a major role as an activator of downstream elements in the pathway critical to the generation of circadian rhythms . The CLOCK gene was first identified in 1997 by Joseph Takahashi and his colleagues. Takahashi used forward mutagenesis screening of mice treated with N-ethyl-N-nitrosourea to create and identify mutations in key genes that broadly affect circadian activity. The CLOCK mutants discovered through
2430-508: Is necessary for normal circadian function. Furthermore, it suggested that the CLOCK-BMAL1 dimer need not exist to modulate other elements of the circadian pathway. Neuronal PAS domain containing protein 2 ( NPAS2 , a CLOCK paralog ) can substitute for CLOCK in these Clock -null mice. Mice with one NPAS2 allele showed shorter periods at first, but eventual arrhythmic behavior. In humans, a polymorphism in Clock , rs6832769, may be related to
2520-563: Is necessary to rescue circadian rhythms in Clock mutants. The CLOCK-BMAL dimer is involved in regulation of other genes and feedback loops. An enzyme SIRT1 also binds to the CLOCK-BMAL complex and acts to suppress its activity, perhaps by deacetylation of Bmal1 and surrounding histones . However, SIRT1's role is still controversial and it may also have a role in deacetylating PER protein, targeting it for degradation. The CLOCK-BMAL dimer acts as
2610-455: Is not sufficient to rescue rhythmicity. Transfection of these cells with both the promoter and the first intron is required for restoration of circadian rhythms in these cells. There is evidence that CRY1 can play a role in how sleep-wake patterns can be inherited through families. There is a mutation, CRY1Δ11 , that causes a delay in one's circadian rhythm. CRY1Δ11 is a splicing variant that has deleted an auto-inhibitory section of
2700-440: Is probably of Romani origin but commonly believed to be a backronym of "council-housed and violent". Similarly, the distress signal SOS is often believed to be an abbreviation for "save our ship" or "save our souls" but was chosen because it has a simple and unmistakable Morse code representation – three dots, three dashes, and three dots, sent without any pauses between characters. More recent examples include
2790-521: The Amber Alert missing-child program was named after Amber Hagerman , a nine-year-old girl who was abducted and murdered in 1996. Officials later publicized the backronym "America's Missing: Broadcast Emergency Response". An example of a backronym as a mnemonic is the Apgar score , used to assess the health of newborn babies. The rating system was devised by and named after Virginia Apgar . Ten years after
CLOCK - Misplaced Pages Continue
2880-480: The Arabidopsis (6-4) photolyase protein. Based on the role of cryptochromes in the entrainment of mammalian circadian rhythms, current researchers hypothesize that they developed simultaneously with the coevolution of PER, TIM, CLOCK , and CYCLE proteins, but there is currently insufficient evidence to determine the exact evolution timing and mechanism of evolution. All members of the flavoprotein superfamily have
2970-759: The Cry gene also cycles with a similar trend. CRY protein levels, however, cycle in a different manner than Cry transcription and mRNA levels. In LD, CRY protein has low levels in light and high levels in dark, and, in DD, CRY levels increase continuously throughout the subjective day and night. Thus, CRY expression is regulated by the clock at the transcriptional level and by light at the translational and posttranslational level. Overexpression of Cry also affects circadian light responses. In Drosophila , Cry overexpression increases flies' sensitivity to low-intensity light. This light regulation of CRY protein levels suggests that CRY has
3060-640: The G2/M checkpoint, and the depletion of CRY1 leads to effects on DNA repair networks, including mismatch repair, UV, and nucleotide excision . In cancer , CRY1 is stabilized by DNA damage, which results in CRY1 expression being associated with worse outcomes in prostate cancer . Because of its role in DNA repair and being pro-tumorigenic , further research can use CRY1 as a therapeutic target . Variants of CRY1 can have impacts on humans in regards to metabolic output. According to
3150-527: The Nampt gene, which codes for the NAMPT protein. NAMPT is part of a series of enzymatic reactions that covert niacin (also called nicotinamide ) to NAD . SIRT1, which requires NAD for its enzymatic activity, then uses increased NAD levels to suppress BMAL1 through deacetylation. This suppression results in less transcription of the NAMPT, less NAMPT protein, less NAD made, and therefore less SIRT1 and less suppression of
3240-528: 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 genes CRY1 and CRY2 encode the proteins CRY1 and CRY2, respectively. Cryptochromes are classified into plant Cry and animal Cry. Animal Cry can be further categorized into insect type (Type I) and mammal-like (Type II). CRY1
3330-556: The epigenetics of the Clock gene may lead to an increased risk of breast cancer . It was found that in women with breast cancer, there was significantly less methylation of the Clock promoter region. It was also noted that this effect was greater in women with estrogen and progesterone receptor-negative tumors. The CLOCK gene may also be a target for somatic mutations in microsatellite unstable colorectal cancers . In one study, 53% of microsatellite instability colorectal cancer cases contained somatic CLOCK mutations. Nascent research in
3420-454: The insect-vertebrate split roughly 500 mya. WC1, an analog of CLOCK/BMAL1 found in fungal genomes, is a proposed candidate common ancestor predating the fungi-animal split . A BLAST search conducted in a 2004 review of clock gene evolution suggested the Clock gene may have arisen from a duplication in the BMAL1 gene, though this hypothesis remains speculative. Another theory alternatively proposes
3510-945: The personality trait agreeableness . Another single nucleotide polymorphism (SNP) in Clock , 3111C, associated with diurnal preference, is also associated with increased insomnia , difficulty losing weight, and recurrence of major depressive episodes in patients with bipolar disorder . In mice, Clock has been implicated in sleep disorders , metabolism , pregnancy , and mood disorders . Clock mutant mice sleep less than normal mice each day. The mice also display altered levels of plasma glucose and rhythms in food intake. These mutants develop metabolic syndrome symptoms over time. Furthermore, Clock mutants demonstrate disrupted estrous cycles and increased rates of full-term pregnancy failure. Mutant Clock has also been linked to bipolar disorder-like symptoms in mice, including mania and euphoria . Clock mutant mice also exhibit increased excitability of dopamine neurons in reward centers of
3600-651: The photoreceptor neurons of birds' eyes are involved in magnetic orientation during migration . Cryptochromes are also thought to be essential for the light-dependent ability of Drosophila to sense magnetic fields . Magnetic fields were once reported to affect cryptochromes also in Arabidopsis thaliana plants: growth behavior seemed to be affected by magnetic fields in the presence of blue (but not red) light. Nevertheless, these results have later turned out to be irreproducible under strictly controlled conditions in another laboratory, suggesting that plant cryptochromes do not respond to magnetic fields. Cryptochrome forms
3690-470: The promoters of the Cry2 and Per genes and activate their transcription. The CRY2 and PER proteins then bind to each other, enter the nucleus, and inhibit CLOCK-BMAL1-activated transcription. The overall function of CRY2 is therefore to repress transcription of CLOCK and BMAL1. Cry1 encodes the CRY1 protein which is a mammalian circadian photoreceptor. In mice, Cry1 expression displays circadian rhythms in
CLOCK - Misplaced Pages Continue
3780-689: The suprachiasmatic nucleus , a brain region involved in the generation of circadian rhythms, with mRNA levels peaking during the light phase and reaching a minimum in the dark. These daily oscillations in expression are maintained in constant darkness. While CRY1 has been well established as a TIM homolog in mammals, the role of CRY1 as a photoreceptor in mammals has been controversial. Early papers indicated that CRY1 has both light-independent and -dependent functions. A study conducted by Selby CP et al. (2000) found that mice without rhodopsin but with cryptochrome still respond to light; however, in mice without either rhodopsin or cryptochrome, c-Fos transcription,
3870-536: The (6-4) photolyase proteins than to plant cryptochrome proteins. It is therefore likely that plant and animal cryptochrome proteins show a unique case of convergent evolution by repeatedly evolving new functions independently of each other from a single common ancestral cry gene. Research by Worthington et al. (2003) indicates that cryptochromes first evolved in bacteria and were identified in Vibrio cholerae . Genome sequencing of this bacteria identified three genes in
3960-515: The C-terminal end, due to the changes in genome and appearance that result from the lack of DNA repair enzymes . The Ramachandran plot shows that the secondary structure of the CRY1 protein is primarily a right-handed alpha helix with little to no steric overlap. The structure of CRY1 is almost entirely made up of alpha helices, with several loops and few beta sheets . In plants, cryptochromes mediate phototropism , or directional growth toward
4050-580: The C-terminus and the given phosphorylated segment could then liberate the transcription factor HY5 by competing for the same binding site at the negative regulator of photomorphogenesis COP1 . A different mechanism may function in Drosophila . The true ground state of the flavin cofactor in Drosophila CRY is still debated, with some models indicating that the FAD is in an oxidized form, while others support
4140-458: The CLOCK protein. This mutation causes dominant effects: half of the heterozygous flies with this mutant gene have a lengthened period of 24.8 hours, while the other half become arrhythmic. Homozygous flies lose their circadian rhythm. Furthermore, the same researchers demonstrated that these mutant flies express low levels of PER and TIM proteins, indicating that Clock functions as a positive element in
4230-504: The CLOCK-BMAL dimer. This dimer can again positively activate the Nampt gene transcription and the cycle continues, creating another oscillatory loop involving CLOCK-BMAL as positive elements. The key role that Clock plays in metabolic and circadian loops highlights the close relationship between metabolism and circadian clocks. The first circadian rhythms were most likely generated by light-driven cell division cycles in ancestral prokaryotic species. This proto-rhythm later evolved into
4320-471: The CRY pathway, in which it is believed that the rhodopsin pathway is providing some light input. Recently, it has also been shown that there is a CRY-mediated light response that is independent of the classical circadian CRY-TIM interaction. This mechanism is believed to require a flavin redox -based mechanism that is dependent on potassium channel conductance. This CRY-mediated light response has been shown to increase action potential firing within seconds of
4410-609: The E-box regulatory elements. PER and CRY proteins accumulate and dimerize during subjective night, and translocate into the nucleus to interact with the CLOCK:BMAL1 complex, directly inhibiting their own expression. This research has been conducted and validated through crystallographic analysis. CLOCK exhibits histone acetyl transferase (HAT) activity, which is enhanced by dimerization with BMAL1. Dr. Paolo Sassone-Corsi and colleagues demonstrated in vitro that CLOCK mediated HAT activity
4500-562: The E-boxes of per and tim , essentially blocking per and tim transcription. CLK is hyperphosphorylated when doubletime (DBT) kinase interacts with the CLK-CYC complex in a PER reliant manner, destabilizing both CLK and PER, leading to the degradation of both proteins. Hypophosphorylated CLK then accumulates, binds to the E-boxes of per and tim and activates their transcription once again. This cycle of post-translational phosphorylation suggest that temporal phosphorylation of CLK helps in
4590-407: The HY4 gene of the plant Arabidopsis thaliana was necessary for the plant's blue light sensitivity, and, when the gene was sequenced in 1993, it showed high sequence homology with photolyase , a DNA repair protein activated by blue light. Reference sequence analysis of cryptochrome-1 isoform d shows two conserved domains with photolyase proteins. Isoform d nucleotide positions 6 through 491 show
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#17328509731814680-699: The NPAS2 gene as the paralog of CLOCK that performs a similar role in the circadian rhythm pathway but in different tissues. Allelic variations within the Clock1a gene in particular are hypothesized to have effects on seasonal timing according to a 2014 study conducted in a population of cyprinid fishes. Polymorphisms in the gene mainly affect the length of the PolyQ domain region, providing an example of divergent evolution where species sharing an ecological niche will partition resources in seasonally variable environments. The length of
4770-553: The PMTR of the chicken iris striated muscle occurs with CRY gene activation by 430 nm blue light. The PMTR was inhibited in CRY gene knockouts and decreased when flavin reductase was inhibited, but remained intact with the addition of melanopsin antagonists. Similarly, cytosolic CRY1 and CRY2 proteins were found in iris myotubes , and decreasing transcription of these genes inhibited PMTRs. The greatest iris PMTRs therefore correspond with
4860-641: The PolyQ domain is associated with changes in transcription level of CLOCK. On average, longer allele lengths were correlated with recently derived species and earlier-spawning species, most likely due to seasonal changes in water temperature. The researchers hypothesize that the length of the domain may serve to compensate for changes in temperature by altering the rate of CLOCK transcription. All other amino acids remained identical across native species, indicating that functional constraint may be another factor influencing CLOCK gene evolution in addition to gene duplication and diversification . One 2017 study investigating
4950-401: The allele become arrhythmic. In both heterozygotes and homozygotes, this mutation also produces lengthened periods and arrhythmicity at the single-cell level. Clock -/- null mutant mice, in which Clock has been knocked out, display completely normal circadian rhythms. The discovery of a null Clock mutant with a wild-type phenotype directly challenged the widely accepted premise that Clock
5040-565: The amplitude of circadian rhythms. The mouse homolog to the Jrk mutant is the ClockΔ19 mutant that possesses a deletion in exon 19 of the Clock gene. This dominant-negative mutation results in a defective CLOCK-BMAL dimer, which causes mice to have a decreased ability to activate per transcription. In constant darkness, ClockΔ19 mice heterozygous for the Clock mutant allele exhibit lengthened circadian periods, while ClockΔ19/Δ19 mice homozygous for
5130-497: The arrhythmicity of these protein levels, cry mutants still showed rhythmicity in overall behavior but could not entrain to short pulses of light, leading researchers to conclude that the dorsal and ventral lateral neurons (the primary pacemaker cells of Drosophila) were still functioning effectively. When cry mutants also had visually unresponsive compound eyes, though, they failed to behaviorally entrain to environmental cues . These findings led researchers to conclude that
5220-537: The backronym "everyone deserves a game above reproach". Many United States Congress bills have backronyms as their names; examples include the USA PATRIOT Act (Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act) of 2001, and the DREAM Act (Development, Relief, and Education for Alien Minors Act). Sometimes a backronym is reputed to have been used in
5310-477: The binding of CRY to other clock gene products, PER and TIM , in a light-dependent manner. Once bound by dCRY, dTIM is committed to degradation by the ubiquitin- proteasome system. Although light pulses do not entrain, full photoperiod LD cycles can still drive cycling in the ventral - lateral neurons in the Drosophila brain. These data along with other results suggest that CRY is the cell-autonomous photoreceptor for body clocks in Drosophila and may play
5400-439: The brain. These results have led Colleen McClung to propose using Clock mutant mice as a model for human mood and behavior disorders. The CLOCK-BMAL dimer has also been shown to activate reverse-erb receptor alpha ( Rev-ErbA alpha ) and retinoic acid orphan receptor alpha ( ROR-alpha ). REV-ERBα and RORα regulate Bmal by binding to retinoic acid-related orphan receptor response elements (ROREs) in its promoter. Variations in
5490-473: The brand name Adidas , named after company founder Adolf "Adi" Dassler but falsely believed to be an acronym for "all day I dream about sport". The word Wiki is said to stand for "what I know is", but in fact is derived from the Hawaiian phrase wiki-wiki meaning 'fast'. Yahoo! , sometimes claimed to mean "yet another hierarchical officious oracle", in fact was chosen because Yahoo's founders liked
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#17328509731815580-430: The characteristics of an N-terminal photolyase homology (PHR) domain. The PHR domain can bind to the flavin adenine dinucleotide (FAD) cofactor and a light-harvesting chromophore . The structure of cryptochrome involves a fold very similar to that of photolyase, arranged as an orthogonal bundle with a single molecule of FAD noncovalently bound to the protein. These proteins have variable lengths and surfaces on
5670-475: The circadian clock, while in mammals, cryptochromes (CRY1 and CRY2) act as transcription repressors within the circadian clockwork. Some insects, including the monarch butterfly , have both a mammal-like and a Drosophila -like version of cryptochrome, providing evidence for an ancestral clock mechanism involving both light-sensing and transcriptional-repression roles for cryptochrome. Cry mutants have altered circadian rhythms, showing that Cry affects
5760-471: The circadian loop. While the mutation affects the circadian clock of the fly, it does not cause any physiological or behavioral defects. The similar sequence between Jrk and its mouse homolog suggests common circadian rhythm components were present in both Drosophila and mice ancestors. A recessive allele of Clock leads to behavioral arrhythmicity while maintaining detectable molecular and transcriptional oscillations. This suggests that Clk contributes to
5850-553: The circadian pacemaker. Drosophila with mutated Cry exhibit little to no mRNA cycling. A point mutation in cry , which is required for flavin association in CRY protein, results in no PER or TIM protein cycling in either DD or LD. In addition, mice lacking Cry1 or Cry2 genes exhibit differentially altered free running periods, but are still capable of photoentrainment . However, mice that lack both Cry1 and Cry2 are arrhythmic in both LD and DD and always have high Per1 mRNA levels. These results suggest that cryptochromes play
5940-457: The cryptochrome protein encoded by cry is necessary for Drosophila photoentrainment. In mammals, a protein analog of the Drosophila cryptochrome protein was discovered with the characteristic property of lacking photolyase activity, prompting researchers to consider it in the same class of cryptochrome proteins. In mice, the greatest cry1 expression is observed in the suprachiasmatic nucleus (SCN) where levels rhythmically fluctuate. Due to
6030-442: The development of striated, rather than smooth, muscle fibers through CRY -mediated PMTRs. Studies in animals and plants suggest that cryptochromes play a pivotal role in the generation and maintenance of circadian rhythms. Similarly, cryptochromes play an important role in the entrainment of circadian rhythms in plants. In Drosophila , cryptochrome (dCRY) acts as a blue-light photoreceptor that directly modulates light input into
6120-686: The early history of the Earth’s formation, such as UV irradiation, may have led to the diversification of clock genes in prokaryotes in response to drastic changes in climate. Cryptochromes , light-sensitive proteins regulated by Cry genes , are most likely descendents of kaiC resulting from a genome duplication predating the Cambrian explosion and are responsible for negative regulation of circadian clocks. Other distinct clock gene lineages arose early in vertebrate evolution, with gene BMAL1 paralogous to CLOCK. Their common ancestor, however, most likely predated
6210-452: The expression of circadian genes in adipose tissue suggests that suppression of the CLOCK gene may causally correlate not only with obesity, but also with type 2 diabetes, with quantitative physical responses to circadian food intake as potential inputs to the clock system. Backronym A normal acronym is a word derived from the initial letters of the words of a phrase, such as radar from "radio detection and ranging". By contrast,
6300-404: The eyes of most animals use photo-sensitive opsins expressed in photoreceptor cells, which communicate information about light from the environment to the nervous system. However, A. queenslandica lacks a nervous system, like other sponges . And it does not have an opsin gene in its fully sequenced genome either, despite having many other G-protein-coupled receptors (GPCRs). Therefore,
6390-450: The focus of several current efforts in optogenetics . Employing transfection , initial studies on yeast have capitalized on the potential of CRY2 heterodimerization to control cellular processes, including gene expression , by light. Although Charles Darwin first documented plant responses to blue light in the 1880s, it was not until the 1980s that research began to identify the pigment responsible. In 1980, researchers discovered that
6480-563: The formation of the original word, and amounts to a false etymology or an urban legend . Acronyms were rare in the English language before the 1930s, and most etymologies of common words or phrases that suggest origin from an acronym are false. Examples include posh , an adjective describing stylish items or members of the upper class. A popular story derives the word as an acronym from "port out, starboard home", referring to 19th-century first-class cabins on ocean liners , which were shaded from
6570-482: The gene. It causes a delay by increasing the affinity of CLOCK and BMAL which in turn lengthens the period. This causes people with this mutation to have a later sleep midpoint than the rest of the population, causing a disorder known as delayed sleep–wake phase disorder . CRY1 is also a key modulator in DNA repair , specifically through temporal regulation. CRY1 has an impact in the cell cycle progression, particularly in
6660-613: The initial publication, the backronym APGAR was coined in the US as a mnemonic learning aid: appearance, pulse, grimace, activity, and respiration. Another example is the American Contract Bridge League's tools to address cheating in online bridge games. EDGAR was originally named for Edgar Kaplan, whose many contributions to the game included groundbreaking efforts to reduce illegal partnership communication. The new EDGAR tools expected to debut in early 2024 have been launched with
6750-425: The lifetime of the activated form of cryptochrome. Activation of cryptochrome may affect the light-sensitivity of retinal neurons, with the overall result that the animal can sense the magnetic field. Animal cryptochromes and closely related animal (6-4) photolyases contain a longer chain of electron-transferring tryptophans than other proteins of the cryptochrome-photolyase superfamily (a tryptophan tetrad instead of
6840-463: The photolyase/cryptochrome family, all of which have the folate and flavin cofactors characteristic of these proteins. Of these genes, one encodes a photolyase, while the other two encode cryptochrome proteins designated VcCry1 and VcCry2. Cashmore AR et al. (1999) hypothesize that mammalian cryptochromes developed later in evolutionary history shortly after plants and animals diverged based on conserved genomic domains between animal cryptochromes and
6930-509: The repair of UV-induced DNA damage . In eukaryotes , cryptochromes no longer retain this original enzymatic activity. By using a T-DNA labeled allele of the cry1 gene in the Arabidopsis plant, researchers determined that the cry1 gene encoded a flavoprotein without photolyase activity and with a unique C-terminal tail . The protein encoded by this gene was named cryptochrome 1 to distinguish it from its ancestral photolyase proteins and
7020-409: The role of CLOCK expression in neurons determined its function in regulating transcriptional networks that could provide insight into human brain evolution. The researchers synthesized differentiated human neurons in vitro and then performed gene knockdown to test the effect of CLOCK on neuronal cell signaling. When CLOCK activity was disrupted, increased neuronal migration of tissue in the neocortex
7110-576: The role of the SCN as the primary mammalian pacemaker as well as the rhythmic fluctuations in cry1 expression, researchers concluded cry1 was also necessary for the entrainment of mammalian circadian rhythms. A common misconception in the evolutionary history of cryptochrome proteins is that mammalian and plant proteins are orthologs of each other that evolved directly from a shared photolyase gene. However, genomic analysis indicates that mammalian and fly cryptochrome proteins show greater sequence similarity to
7200-531: The screen displayed an abnormally long period of daily activity. This trait proved to be heritable . Mice bred to be heterozygous showed longer periods of 24.4 hours compared to the control 23.3 hour period. Mice homozygous for the mutation showed 27.3 hour periods, but eventually lost all circadian rhythmicity after several days in constant darkness. That showed that "intact CLOCK genes" are necessary for normal mammalian circadian function, as these mutations were semidominant. CLOCK protein has been found to play
7290-486: The sponge's unique eyes must have evolved a different mechanism to detect light and mediate phototaxis, possibly with cryptochromes or other proteins. Isolated irises constrict in response to light via a photomechanical transduction response (PMTR) in a variety of species and require either melanopsin or cryptochrome to do so. The iris of chicken embryos senses short-wavelength light via a cryptochrome, rather than opsins. Research by Margiotta and Howard (2020) shows that
7380-401: The sun on outbound voyages east (e.g. from Britain to India ) and homeward voyages west. The word's actual etymology is unknown, but more likely related to Romani påš xåra ('half-penny') or to Urdu (borrowed from Persian ) safed-pōśh ('white robes'), a term for wealthy people. Another example is the word chav , which is a derogatory term for a working-class youth. This word
7470-596: The switch from the vegetative to the flowering stage of development. In Arabidopsis , CRY1 is the primary inhibitor of hypocotyl elongation but CRY2 inhibits hypocotyl elongation under low blue light intensity. CRY2 promotes flowering under long-day conditions. CRY gene mediates photomorphogenesis in several ways. CRY C-terminal interacts with CONTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a E3 ubiquitin ligase that represses photomorphogenesis and flowering time. The interaction inhibits COP1 activity and allows transcription factors such as ELONGATED HYPOCOTYL 5 (HY5) to accumulate. HY5
7560-429: The timing mechanism of the circadian clock. A similar model is found in mice, in which BMAL1 dimerizes with CLOCK to activate per and cryptochrome ( cry ) transcription. PER and CRY proteins form a heterodimer which acts on the CLOCK-BMAL heterodimer to repress the transcription of per and cry . The heterodimer CLOCK:BMAL1 functions similarly to other transcriptional activator complexes; CLOCK:BMAL1 interacts with
7650-454: The topic, cryptochrome photoreception and phototransduction in Drosophila and Arabidopsis thaliana is still poorly understood. Cryptochromes are known to possess two chromophores: pterin (in the form of 5,10-methenyltetrahydrofolic acid (MTHF)) and flavin (in the form of FAD). Both may absorb a photon , and in Arabidopsis , pterin appears to absorb at a wavelength of 380 nm and flavin at 450 nm. Past studies have supported
7740-589: The transduction of a light signal into a chemical signal in plant cryptochromes, which could be triggered by a photo-induced negative charge on the FAD cofactor or on the neighboring aspartic acid within the protein. This negative charge would electrostatically repel the protein-bound ATP molecule and thereby also the protein C-terminal domain, which covers the ATP binding pocket prior to photon absorption. The resulting change in protein conformation could lead to phosphorylation of previously inaccessible phosphorylation sites on
7830-415: The wild-type protein. The presence of an antimorphic protein downregulates the transcriptional products normally upregulated by Clock . In Drosophila , a mutant form of Clock ( Jrk ) was identified by Allada, Hall , and Rosbash in 1998. The team used forward genetics to identify non-circadian rhythms in mutant flies. Jrk results from a premature stop codon that eliminates the activation domain of
7920-594: The word's meaning of "rude, unsophisticated, uncouth" (taken from Jonathan Swift 's book Gulliver's Travels ). The distress call " pan-pan " is commonly stated to mean "possible assistance needed", whereas it is in fact derived from the French word panne , meaning 'breakdown'. Cryptochrome 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
8010-500: Was found to be involved in the photoreception of blue light. Studies of Drosophila cry- knockout mutants led to the later discovery that cryptochrome proteins are also involved in regulating the mammalian circadian clock. The Drosophila cry gene similarly encodes a flavoprotein without photolyase activity that also binds pterin chromophores . Cry mutants ( cry ) were found to express arrhythmic levels of luciferase as well as PER and TIM proteins in photoreceptor cells. Despite
8100-471: Was observed, suggesting a molecular mechanism for cortical expansion unique to human brain development. However, the precise role of CLOCK in metabolic regulation of cortical neurons remains to be determined. Another study looking at the relationship between CLOCK polymorphisms in the 3’ flanking region and morning/evening preference in adults found a correlation between subjects with the 3111C allele and preference for evening hours based on answers provided in
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