Cryptochrome - Knowledge

1537: 854:(HY5) to accumulate. HY5 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 1588:

triad). The longer chain leads to a better separation and over 1000× longer lifetimes of the photoinduced flavin-tryptophan radical pairs than in proteins with a triad of tryptophans. The absence of spin-selective recombination of these radical pairs on the nanosecond to microsecond timescales seems to be incompatible with the suggestion that magnetoreception by cryptochromes is based on the forward light reaction.

40: 1587:

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 a

1582:

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

1367:

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

853:

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

830:

plants increases blue-light-stimulated cotyledon expansion, which results in many broad leaves and no flowers rather than 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

1196:

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 the binding of CRY to other clock gene products,

927:

A new hypothesis proposes that partner molecules sense 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

1382:

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 is hard to measure its capacity as purely a photoreceptor. However, some recent studies indicate that

1228:

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 the CRY pathway, in which it is believed that the rhodopsin pathway is providing some light

936:

binding pocket prior to photon absorption. The resulting change in protein conformation could lead to phosphorylation of previously inaccessible phosphorylation sites on the C-terminus and the given phosphorylated segment could then liberate the transcription factor HY5 by competing for the same

700:

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

1570:

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

1269:

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

501:, 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 2340:"Double loss-of-function mutation in EARLY FLOWERING 3 and CRYPTOCHROME 2 genes delays flowering under continuous light but accelerates it under long days and short days: an important role for Arabidopsis CRY2 to accelerate flowering time in continuous light" 538:

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

1342:

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.

904:, pterin appears to absorb at a wavelength of 380 nm and flavin at 450 nm. Past studies have supported a model by which energy captured by pterin is transferred to flavin. Under this model of phototransduction, FAD would then be 1104:

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

1071:

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 the PMTR of the chicken iris striated muscle occurs with

1364:, 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. 1260:

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 the

4679:

Müller P, Yamamoto J, Martin R, Iwai S, Brettel K (November 2015). "Discovery and functional analysis of a 4th electron-transferring tryptophan conserved exclusively in animal cryptochromes and (6-4) photolyases".

705:(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, 2026:

Todo T, Ryo H, Yamamoto K, Toh H, Inui T, Ayaki H, et al. (April 1996). "Similarity among the Drosophila (6-4)photolyase, a human photolyase homolog, and the DNA photolyase-blue-light photoreceptor family".

1583:

field's effect on the correlation (parallel or anti-parallel) of these radicals, which affects the lifetime of the activated form of cryptochrome. Activation of cryptochrome may affect the light-sensitivity of

482:

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 the HY4 gene of the plant

647:

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

1696:

van der Spek PJ, Kobayashi K, Bootsma D, Takao M, Eker AP, Yasui A (October 1996). "Cloning, tissue expression, and mapping of a human photolyase homolog with similarity to plant blue-light receptors".

426:

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 is a circadian

1229:

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

1224:

and may play 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

1289:

overexpression increases flies' sensitivity to low-intensity light. This light regulation of CRY protein levels suggests that CRY has a circadian role upstream of other clock genes and components.

576:. The protein encoded by this gene was named cryptochrome 1 to distinguish it from its ancestral photolyase proteins and was found to be involved in the photoreception of blue light. Studies of 2480:

Song SH, Dick B, Penzkofer A, Pokorny R, Batschauer A, Essen LO (October 2006). "Absorption and fluorescence spectroscopic characterization of cryptochrome 3 from Arabidopsis thaliana".

1092:, and decreasing transcription of these genes inhibited PMTRs. The greatest iris PMTRs therefore correspond with the development of striated, rather than smooth, muscle fibers through 4718:

Cailliez F, Müller P, Firmino T, Pernot P, de la Lande A (February 2016). "Energetics of Photoinduced Charge Migration within the Tryptophan Tetrad of an Animal (6-4) Photolyase".

1548:

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 the

850:, 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. 1109:, cryptochrome (dCRY) acts as a blue-light photoreceptor that directly modulates light input into the circadian clock, while in mammals, cryptochromes (CRY1 and CRY2) act as 1059:(GPCRs). Therefore, the sponge's unique eyes must have evolved a different mechanism to detect light and mediate phototaxis, possibly with cryptochromes or other proteins. 747:

bound to the protein. These proteins have variable lengths and surfaces on the C-terminal end, due to the changes in genome and appearance that result from the lack of

2663:

Cailliez F, Müller P, Gallois M, de la Lande A (September 2014). "ATP binding and aspartate protonation enhance photoinduced electron transfer in plant cryptochrome".

1124:-like version of cryptochrome, providing evidence for an ancestral clock mechanism involving both light-sensing and transcriptional-repression roles for cryptochrome. 1464:

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

831:

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.

506: 2303:

Hsu DS, Zhao X, Zhao S, Kazantsev A, Wang RP, Todo T, et al. (November 1996). "Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteins".

671:

of each other that evolved directly from a shared photolyase gene. However, genomic analysis indicates that mammalian and fly cryptochrome proteins show greater

981:• by light. Furthermore, mutations that blocked photoreduction had no effect on light-induced degradation of CRY, while mutations that altered the stability of 216: 63: 675:

to 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

4375:

Ahmad M, Galland P, Ritz T, Wiltschko R, Wiltschko W (February 2007). "Magnetic intensity affects cryptochrome-dependent responses in Arabidopsis thaliana".

1314:

Cryptochrome is one of the four groups of mammalian clock genes/proteins that generate a transcription-translation negative-feedback loop (TTFL), along with

1173:

mRNA levels. These results suggest that cryptochromes play a photoreceptive role, as well as acting as negative regulators of Per gene expression in mice.

952:

CRY is still debated, with some models indicating that the FAD is in an oxidized form, while others support a model in which the flavin cofactor exists in

1080:

gene knockouts and decreased when flavin reductase was inhibited, but remained intact with the addition of melanopsin antagonists. Similarly, cytosolic

3776:"Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals" 743:. The structure of cryptochrome involves a fold very similar to that of photolyase, arranged as an orthogonal bundle with a single molecule of FAD 4850: 656:(SCN) where levels rhythmically fluctuate. Due to the role of the SCN as the primary mammalian pacemaker as well as the rhythmic fluctuations in 4802: 3560:

Busza A, Emery-Le M, Rosbash M, Emery P (June 2004). "Roles of the two Drosophila CRYPTOCHROME structural domains in circadian photoreception".

1149:

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

784:, or directional growth toward a light source, in response to blue light. This response is now known to have its own set of photoreceptors, the 4768: 1465: 1067:

Isolated irises constrict in response to light via a photomechanical transduction response (PMTR) in a variety of species and require either

4975: 4970: 2010: 580:

knockout mutants led to the later discovery that cryptochrome proteins are also involved in regulating the mammalian circadian clock. The

2198:"Purification and characterization of three members of the photolyase/cryptochrome family blue-light photoreceptors from Vibrio cholerae" 4924: 240: 87: 3096:

Somers DE, Devlin PF, Kay SA (November 1998). "Phytochromes and cryptochromes in the entrainment of the Arabidopsis circadian clock".

2384:"The blue light receptor CRY1 interacts with GID1 and DELLA proteins to repress GA signaling during photomorphogenesis in Arabidopsis" 1926:

Ahmad M, Cashmore AR (November 1993). "HY4 gene of A. thaliana encodes a protein with characteristics of a blue-light photoreceptor".

489:

was necessary for the plant's blue light sensitivity, and, when the gene was sequenced in 1993, it showed high sequence homology with

4605:"Light-activated cryptochrome reacts with molecular oxygen to form a flavin-superoxide radical pair consistent with magnetoreception" 4114:"An observational study investigating the CRY1Δ11 variant associated with delayed sleep-wake patterns and circadian metabolic output" 3367:"CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity" 893: 843:. They help control seed and seedling development, as well as the switch from the vegetative to the flowering stage of development. 1233:-based mechanism that is dependent on potassium channel conductance. This CRY-mediated light response has been shown to increase 1036:

expressed in photoreceptor cells, which communicate information about light from the environment to the nervous system. However,

1029:

express a blue-light-sensitive cryptochrome (Aq-Cry2), which might mediate phototaxis. In contrast, the eyes of most animals use

616: 544: 228: 75: 763:

with little to no steric overlap. The structure of CRY1 is almost entirely made up of alpha helices, with several loops and few

725: 221: 68: 4909: 3522:

Griffin EA, Staknis D, Weitz CJ (October 1999). "Light-independent role of CRY1 and CRY2 in the mammalian circadian clock".

1378:

as the main circadian photoreceptor, in particular melanopsin cells that mediate entrainment and communication between the

713:

proteins, but there is currently insufficient evidence to determine the exact evolution timing and mechanism of evolution.

2557: 692:. Genome sequencing of this bacteria identified three genes in the photolyase/cryptochrome family, all of which have the 4985: 3244:"Cryptochromes define a novel circadian clock mechanism in monarch butterflies that may underlie sun compass navigation" 4843: 1441:

expression) is not sufficient to rescue rhythmicity. Transfection of these cells with both the promoter and the first

1419: 1056: 800: 729: 4420: 667:

A common misconception in the evolutionary history of cryptochrome proteins is that mammalian and plant proteins are

2001:

Thompson CL, Sancar A (2004). "Cryptochrome: Discovery of a Circadian Photopigment". In Lenci F, Horspool WM (ed.).

1220:

brain. These data along with other results suggest that CRY is the cell-autonomous photoreceptor for body clocks in

686:

Research by Worthington et al. (2003) indicates that cryptochromes first evolved in bacteria and were identified in

4990: 1327: 619:

to short pulses of light, leading researchers to conclude that the dorsal and ventral lateral neurons (the primary

2148:

Cashmore AR, Jarillo JA, Wu YJ, Liu D (April 1999). "Cryptochromes: blue light receptors for plants and animals".

1475:, specifically through temporal regulation. CRY1 has an impact in the cell cycle progression, particularly in the 493:, a DNA repair protein activated by blue light. Reference sequence analysis of cryptochrome-1 isoform d shows two 4889: 4884: 3835:"Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice" 1518:

in comparison to those with the CRY1Δ11 variant. The participants with the variant had a delayed sleep cycle and

608: 2741:"Formation and function of flavin anion radical in cryptochrome 1 blue-light photoreceptor of monarch butterfly" 4995: 4759: 1110: 744: 737: 2782:"Animal type 1 cryptochromes. Analysis of the redox state of the flavin cofactor by site-directed mutagenesis" 1519: 1491:, CRY1 is stabilized by DNA damage, which results in CRY1 expression being associated with worse outcomes in 4919: 4904: 4899: 2996:

Tu DC, Batten ML, Palczewski K, Van Gelder RN (October 2004). "Nonvisual photoreception in the chick iris".

1361: 1018:

or quartet state by absorption of a photon, which then leads to a conformational change in the CRY protein.

733: 653: 497:

domains with photolyase proteins. Isoform d nucleotide positions 6 through 491 show a conserved domain with

4879: 4836: 1541: 1410:

promoter activation. This delay is independent of CRY1 or CRY2 levels and is mediated by a combination of

1374:

transcription, a mediator of light sensitivity, significantly drops. In recent years, data have supported

933: 929: 443: 3894:"Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity" 1861: 1484: 1456:, that causes a delay in one's circadian rhythm. CRY1Δ11 is a splicing variant that has deleted an 1368:

but with cryptochrome still respond to light; however, in mice without either rhodopsin or cryptochrome,

233: 80: 4949: 4874: 2947:"Cryptochromes Mediate Intrinsic Photomechanical Transduction in Avian Iris and Somatic Striated Muscle" 1271: 427: 399: 345: 298: 145: 4261:"A visual pathway links brain structures active during magnetic compass orientation in migratory birds" 3949:

Hoang N, Schleicher E, Kacprzak S, Bouly JP, Picot M, Wu W, et al. (July 2008). Schibler U (ed.).

1507: 1506:

Variants of CRY1 can have impacts on humans in regards to metabolic output. According to a 2021 study,

1480: 4176:"The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair" 3465:"Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2" 1536: 1158: 4551: 4504: 4384: 4331: 4272: 4239: 4187: 4125: 3905: 3846: 3787: 3673: 3569: 3476: 3306: 3200: 3005: 2841: 2619: 2157: 2036: 1935: 1814: 1496: 1457: 1265:

gene also cycles with a similar trend. CRY protein levels, however, cycle in a different manner than

1201:, in a light-dependent manner. Once bound by dCRY, dTIM is committed to degradation by the ubiquitin- 676: 631:

mutants also had visually unresponsive compound eyes, though, they failed to behaviorally entrain to

485: 2700:"A novel photoreaction mechanism for the circadian blue light photoreceptor Drosophila cryptochrome" 4980: 4765: 4244: 3049:"Novel features of cryptochrome-mediated photoreception in the brain circadian clock of Drosophila" 1575: 956: 913: 756: 4174:

Shafi AA, McNair CM, McCann JJ, Alshalalfa M, Shostak A, Severson TM, et al. (January 2021).

4929: 4408: 4221: 4083: 3951:"Human and Drosophila cryptochromes are light activated by flavin photoreduction in living cells" 3642: 3593: 3445: 3396: 3332: 3224: 3173: 3121: 3029: 2588: 2413: 2060: 1959: 1891: 1773: 1629: 1549: 1331: 992:• destroyed CRY photoreceptor function. These observations provide support for a ground state of 840: 502: 494: 463: 4658:. Beckman Institute for Advanced Science and Technology, University of Illinois Urbana–Champaign 1801:

Brautigam CA, Smith BS, Ma Z, Palnitkar M, Tomchick DR, Machius M, Deisenhofer J (August 2004).

1208:

Although light pulses do not entrain, full photoperiod LD cycles can still drive cycling in the

679:

by repeatedly evolving new functions independently of each other from a single common ancestral

3414:

Stanewsky R, Kaneko M, Emery P, Beretta B, Wager-Smith K, Kay SA, et al. (November 1998).

2433:"Arabidopsis cryptochrome 1 controls photomorphogenesis through regulation of H2A.Z deposition" 4944: 4939: 4808: 4792: 4735: 4697: 4636: 4585: 4556:"Direct observation of a photoinduced radical pair in a cryptochrome blue-light photoreceptor" 4532: 4473: 4400: 4357: 4300: 4213: 4151: 4075: 4031: 3982: 3931: 3874: 3815: 3753: 3699: 3634: 3585: 3539: 3504: 3437: 3388: 3324: 3275: 3216: 3165: 3113: 3078: 3021: 2978: 2918: 2869: 2803: 2762: 2721: 2680: 2645: 2580: 2538: 2517:"Evidence of a light-sensing role for folate in Arabidopsis cryptochrome blue-light receptors" 2497: 2462: 2405: 2361: 2320: 2285: 2229: 2173: 2109: 2052: 2006: 1951: 1883: 1842: 1791: 1765: 1724: 1678: 1649:"Cryptochromes Orchestrate Transcription Regulation of Diverse Blue Light Responses in Plants" 1621: 1500: 1213: 1117: 875: 752: 672: 668: 620: 252: 99: 3463:

Vitaterna MH, Selby CP, Todo T, Niwa H, Thompson C, Fruechte EM, et al. (October 1999).

2256:"Magnetoreception of Photoactivated Cryptochrome 1 in Electrochemistry and Electron Transfer" 1453: 4727: 4689: 4626: 4616: 4575: 4567: 4522: 4512: 4463: 4455: 4392: 4347: 4339: 4290: 4280: 4203: 4195: 4141: 4133: 4112:

Smieszek SP, Brzezynski JL, Kaden AR, Shinn JA, Wang J, Xiao C, et al. (October 2021).

4065: 4021: 4013: 3972: 3962: 3921: 3913: 3864: 3854: 3805: 3795: 3743: 3735: 3689: 3681: 3624: 3577: 3531: 3494: 3484: 3427: 3378: 3314: 3265: 3255: 3208: 3155: 3105: 3068: 3060: 3013: 2968: 2958: 2908: 2900: 2859: 2849: 2793: 2752: 2711: 2672: 2635: 2627: 2572: 2528: 2489: 2452: 2444: 2395: 2351: 2312: 2275: 2267: 2219: 2209: 2165: 2099: 2091: 2044: 1943: 1873: 1832: 1822: 1755: 1714: 1706: 1668: 1660: 1613: 1531: 1234: 1030: 379: 375: 371: 302: 293: 149: 140: 4442:

Harris SR, Henbest KB, Maeda K, Pannell JR, Timmel CR, Hore PJ, Okamoto H (December 2009).

4000:

Sato TK, Yamada RG, Ukai H, Baggs JE, Miraglia LJ, Kobayashi TJ, et al. (March 2006).

4772: 2889:"Blue-light-receptive cryptochrome is expressed in a sponge eye lacking neurons and opsin" 2887:

Rivera AS, Ozturk N, Fahey B, Plachetzki DC, Degnan BM, Sancar A, Oakley TH (April 2012).

1878: 1563: 1511: 1492: 1476: 1198: 917: 909: 859: 811: 688: 467: 322: 169: 4259:

Heyers D, Manns M, Luksch H, Güntürkün O, Mouritsen H (September 2007). Iwaniuk A (ed.).

4054:"Delay in feedback repression by cryptochrome 1 is required for circadian clock function" 2698:

Berndt A, Kottke T, Breitkreuz H, Dvorsky R, Hennig S, Alexander M, Wolf E (April 2007).

701:

animals diverged based on conserved genomic domains between animal cryptochromes and the

438:. In plants, blue-light photoreception can be used to cue developmental signals. Besides 4755: 4508: 4388: 4335: 4276: 4191: 4129: 3909: 3850: 3791: 3677: 3573: 3480: 3310: 3204: 3009: 2845: 2623: 2161: 2040: 1939: 1910: 1818: 4631: 4604: 4580: 4555: 4527: 4492: 4468: 4444:"Effect of magnetic fields on cryptochrome-dependent responses in Arabidopsis thaliana" 4443: 4352: 4319: 4295: 4260: 4208: 4175: 4146: 4113: 4026: 4001: 3977: 3950: 3926: 3893: 3748: 3723: 3694: 3661: 3270: 3243: 3073: 3048: 2973: 2946: 2913: 2888: 2864: 2829: 2640: 2607: 2457: 2432: 2280: 2255: 1673: 1648: 1617: 1579: 1553: 1248:

Cryptochrome, like many genes involved in circadian rhythm, shows circadian cycling in

871: 479: 355: 4788: 3629: 3612: 3432: 3416:"The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila" 3415: 3383: 3366: 3242:

Zhu H, Sauman I, Yuan Q, Casselman A, Emery-Le M, Emery P, Reppert SM (January 2008).

3160: 3143: 3047:

Klarsfeld A, Malpel S, Michard-Vanhée C, Picot M, Chélot E, Rouyer F (February 2004).

2104: 2080:"Characterization of photolyase/blue-light receptor homologs in mouse and human cells" 2079: 1978:"CRY1 cryptochrome circadian regulator 1 [Homo sapiens (human)] - Gene - NCBI" 1837: 1802: 635:. These findings led researchers to conclude that the cryptochrome protein encoded by 4964: 4934: 4817: 4225: 3869: 3834: 3810: 3775: 3499: 3464: 3142:

Emery P, Stanewsky R, Helfrich-Förster C, Emery-Le M, Hall JC, Rosbash M (May 2000).

2592: 2493: 2417: 1803:"Structure of the photolyase-like domain of cryptochrome 1 from Arabidopsis thaliana" 1315: 1015: 604: 359: 3646: 3597: 3400: 3191:

Reppert SM, Weaver DR (August 2002). "Coordination of circadian timing in mammals".

3177: 3125: 3033: 2606:

Müller P, Bouly JP, Hitomi K, Balland V, Getzoff ED, Ritz T, Brettel K (June 2014).

2064: 1777: 1633: 1556:. Cryptochromes are also thought to be essential for the light-dependent ability of 1157:

genes exhibit differentially altered free running periods, but are still capable of

611:

proteins in photoreceptor cells. Despite the arrhythmicity of these protein levels,

4863: 4087: 3449: 3336: 3228: 3064: 1963: 1895: 1423: 921: 807: 781: 710: 697: 555: 513: 459: 455: 439: 394: 3739: 3109: 2576: 2338:

Nefissi R, Natsui Y, Miyata K, Oda A, Hase Y, Nakagawa M, et al. (May 2011).

2078:

Kobayashi K, Kanno S, Smit B, van der Horst GT, Takao M, Yasui A (November 1998).

1744:"Phylogenetic and Functional Classification of the Photolyase/Cryptochrome Family" 584:

gene similarly encodes a flavoprotein without photolyase activity that also binds

4412: 4285: 3967: 3535: 3260: 2169: 2048: 888:

is still poorly understood. Cryptochromes are known to possess two chromophores:

269: 116: 4778: 4655: 4052:

Ukai-Tadenuma M, Yamada RG, Xu H, Ripperger JA, Liu AC, Ueda HR (January 2011).

2196:

Worthington EN, Kavakli IH, Berrocal-Tito G, Bondo BE, Sancar A (October 2003).

1356:

encodes the CRY1 protein which is a mammalian circadian photoreceptor. In mice,

803: 792: 785: 764: 760: 740: 632: 588: 564: 388: 332: 179: 4775:, by Steven M. Reppert, Department of Neurobiology, University of Massachusetts 4497: