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Aziz Sancar - One of the best experts on this subject based on the ideXlab platform.
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Photolyase and Cryptochrome Blue-Light Photoreceptors
Advances in Protein Chemistry, 2020Co-Authors: Aziz SancarAbstract:Publisher Summary This chapter focuses on the photolyase/cryptochrome blue-light photoreceptor family that encompasses a large group of proteins from all three biological kingdoms. These proteins absorb near-ultraviolet (UV)/blue light and use the light energy to repair far UV-induced DNA damage to reset the circadian clock. The photolyase/cryptochrome family has three members: photolyase (cyclobutane pyrimidine dimer photolyase), (6–4) photolyase, and cryptochrome. Both photolyase and cryptochrome also perform light-independent functions in DNA repair and in generating the molecular circadian clock, respectively. Photolyases are monomeric proteins of 450–550 amino acids and two noncovalently bound cofactors. Escherichia coli (E. coli) photolyase is made up of two well-defined domains: an N terminal α/β domain (residues 1–132) and a C-terminal α-helical domain. Cryptochromes regulate blue-light-dependent growth and development in plants; Cryptochromes have now been identified in the nonphotosynthetic bacterium Vibrio cholerae (V. cholerae), which has no known photoresponses. Cryptochromes exhibit 20–40% sequence identities to photolyases.
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The Second Chromophore in Drosophila Photolyase/Cryptochrome Family Photoreceptors
Biochemistry, 2011Co-Authors: Christopher P Selby, Aziz SancarAbstract:The photolyase/cryptochrome family of proteins are FAD-containing flavoproteins which carry out blue-light-dependent functions including DNA repair, plant growth and development, and regulation of the circadian clock. In addition to FAD, many members of the family contain a second chromophore which functions as a photoantenna, harvesting light and transferring the excitation energy to FAD and thus increasing the efficiency of the system. The second chromophore is methenyltetrahydrofolate (MTHF) in most photolyases characterized to date and FAD, FMN, or 5-deazariboflavin in others. To date, no second chromophore has been identified in Cryptochromes. Drosophila contains three members of the cryptochrome/photolyase family: cyclobutane pyrimidine dimer (CPD) photolyase, (6–4) photoproduct photolyase, and cryptochrome. We developed an expression system capable of incorporating all known second chromophores into the cognate cryptochrome/photolyase family members. Using this system, we demonstrate that Drosophil...
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comparative photochemistry of animal type 1 and type 4 Cryptochromes
Biochemistry, 2009Co-Authors: Nuri Ozturk, Sang-hun Song, Christopher P Selby, Dongping Zhong, Rui Ye, Aziz SancarAbstract:Cryptochromes are photolyase-like flavoproteins that are known or suspected to function as sensory photoreceptors (1−3). Despite extensive work on the photochemical and photobiological properties of animal CRYs,1 at present, only Drosophila cryptochrome (DmCRY) and some insect CRYs closely related to DmCRY have been shown to function as photosensors (4,5). In an effort to identify other CRYs that have photosensory functions and establish a universal reaction mechanism for all CRYs, we have been isolating and characterizing CRYs from diverse sources. Phylogenetic analyses have divided the cryptochrome/photolyase family into several classes (3−5) including the CPD (cyclobutane pyrimidine dimer) photolyases and the single-stranded DNA-specific photolyases, which use light energy to repair CPDs in DNA, plant CRYs, which regulate growth and development in response to light, and the animal CRYs. Animal CRYs, of which there are several types, are related to the (6-4) photolyases, which use light energy to repair (6-4) photoproducts in DNA. Type 1 CRYs, which include DmCRY, are degraded in vivo in response to exposure to light, and are thought to regulate the circadian clock as a result of their effects on protein stability. Type 2 CRYs are essential components of the circadian clock, in which they function independently of light as repressors of transcription. Type 2 CRYs have failed to show definitive evidence for a photoreceptor function (3). Type 4 CRYs have not been critically examined. However, based on evolutionary considerations as well as expression patterns, it has been proposed that type 4 CRYs function as potential circadian photoreceptors in zebrafish and in the chicken pineal gland (6,7). Indeed, photoentrainment of peripheral organs of zebrafish and of the circadian rhythm of the zebrafish embryonic cell line Z3 by light (8) and in chicken the presence of a vitamin A-independent pineal photosensor (9) and constriction of the embryonic chick pupil by light, independent of opsins (10), have been considered as evidence for cryptochrome-mediated circadian photoreception. Hence, we decided to purify zebrafish and chicken type 4 CRYs and examine their putative photoreceptor activity using type 1 CRYs, which are known to function as photoreceptors, as reference proteins. In this paper, we describe the purification of type 4 CRYs of zebrafish (Danio rerio) (ZfCRY4) and of chicken (Gallus gallus) (GgCRY4) with stoichiometric amounts of the FAD cofactor. In addition, we compare the spectroscopic, photophysical, and photobiological properties of DmCRY and ZfCRY4 as representatives of animal type 1 and type 4 Cryptochromes. We find that the two types of CRYs exhibit distinct excited-state dynamic and photobiological properties. Strikingly, we find that while a light flash of 1 ms duration is sufficient to cause nearly complete proteolysis of DmCRY and that DmCRY is subject to light-induced proteolysis in Drosophila, zebrafish, and mammalian cell lines, ZfCRY4 does not undergo light-induced proteolysis by flash or continuous illumination in either orthologous or heterologous hosts. These results suggest that animal type 1 CRYs which are known to function as photoreceptors and type 4 CRYs which are thought to be photoreceptors have potentially different photosignaling mechanisms.
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analysis of autophosphorylating kinase activities of arabidopsis and human Cryptochromes
Biochemistry, 2006Co-Authors: Sezgin Özgür, Aziz SancarAbstract:Cryptochromes are FAD-based blue-light photoreceptors that regulate growth and development in plants and the circadian clock in animals. Arabidopsis thaliana and humans possess two Cryptochromes. Recently, it was found that Arabidopsis cryptochrome 1 (AtCry1) binds ATP and exhibits autokinase activity that is simulated by blue light. Similarly, it was reported that human cryptochrome 1 (HsCry1) exhibited autophosphorylation activity under blue light. To test the generality of light stimulated kinase function of Cryptochromes, we purified AtCry1, AtCry2, HsCry1, and HsCry2 and probed them for kinase activity under a variety of conditions. We find that AtCry1, which contains near stoichiometric amounts of FAD and human HsCry1 and HsCry2 (which contain only trace amounts of FAD), has autokinase activity, but AtCry2, which also contains stoichiometric amounts of FAD, does not. Finally, we find that the kinase activity of AtCry1 is not significantly affected by light or the redox status of the flavin cofactor.
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Photochemistry and photobiology of cryptochrome blue-light photopigments : The search for a photocycle
Photochemistry and Photobiology, 2005Co-Authors: Carrie L. Partch, Aziz SancarAbstract:Cryptochromes are flavoproteins that exhibit high sequence and structural similarity to the light-dependent DNA-repair enzyme, photolyase. Cryptochromes have lost the ability to repair DNA; instead, they use the energy from near-UV/blue light to regulate a variety of growth and adaptive processes in organisms ranging from bacteria to humans. The photocycle of cryptochrome is not yet known, although it is hypothesized that it may share some similarity to that of photolyase, which utilizes light-driven electron transfer from the catalytic flavin chromophore. In this review, we present genetic evidence for the photoreceptive role of Cryptochromes and discuss recent biochemical studies that have furthered our understanding of the cryptochrome photocycle. In particular, the role of the unique C-terminal domain in cryptochrome phototransduction is discussed.
Klaus Schulten - One of the best experts on this subject based on the ideXlab platform.
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Reaction Kinetics and Mechanism of Magnetic Field Effects in Cryptochrome
The Journal of Physical Chemistry, 2020Co-Authors: Ilia A. Solov’yov, Klaus SchultenAbstract:Creatures as varied as mammals, fish, insects, reptiles, and birds have an intriguing sixth sense that allows them to orient themselves in the Earth’s magnetic field. Despite decades of study, the physical basis of this magnetic sense remains elusive. A likely mechanism is furnished by magnetically sensitive radical pair reactions occurring in the retina, the light-sensitive part of animal eyes. A photoreceptor, cryptochrome, has been suggested to endow birds with magnetoreceptive abilities as the protein has been shown to exhibit the biophysical properties required for an animal magnetoreceptor to operate properly. Here, we propose a theoretical analysis method for identifying cryptochrome’s signaling reactions involving comparison of measured and calculated reaction kinetics in cryptochrome. Application of the method yields an exemplary light-driven reaction cycle, supported through transient absorption and electron-spin-resonance observations together with known facts on avian magnetoreception. The reaction cycle permits one to predict magnetic field effects on cryptochrome activation and deactivation. The suggested analysis method gives insight into structural and dynamic design features required for optimal detection of the geomagnetic field by cryptochrome and suggests further experimental and theoretical studies.
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Reaction Kinetics and Mechanism of Magnetic Field Effects in Cryptochrome
Journal of Physical Chemistry B, 2012Co-Authors: Ilia A. Solov’yov, Klaus SchultenAbstract:Creatures as varied as mammals, fish, insects, reptiles, and birds have an intriguing sixth sense that allows them to orient themselves in the Earth’s magnetic field. Despite decades of study, the physical basis of this magnetic sense remains elusive. A likely mechanism is furnished by magnetically sensitive radical pair reactions occurring in the retina, the light-sensitive part of animal eyes. A photoreceptor, cryptochrome, has been suggested to endow birds with magnetoreceptive abilities as the protein has been shown to exhibit the biophysical properties required for an animal magnetoreceptor to operate properly. Here, we propose a theoretical analysis method for identifying cryptochrome’s signaling reactions involving comparison of measured and calculated reaction kinetics in cryptochrome. Application of the method yields an exemplary light-driven reaction cycle, supported through transient absorption and electron-spin-resonance observations together with known facts on avian magnetoreception. The rea...
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Decrypting cryptochrome: Revealing the molecular identity of the photoactivation reaction
Journal of the American Chemical Society, 2012Co-Authors: Ilia A. Solov'yov, Abdul Rehaman Moughal Shahi, Tatiana Domratcheva, Klaus SchultenAbstract:Migrating birds fly thousands of miles or more, often without visual cues and in treacherous winds, yet keep direction. They employ for this purpose, apparently as a powerful navigational tool, the photoreceptor protein cryptochrome to sense the geomagnetic field. The unique biological function of cryptochrome supposedly arises from a photoactivation reaction involving radical pair formation through electron transfer. Radical pairs, indeed, can act as a magnetic compass; however, the cryptochrome photoreaction pathway is not fully resolved yet. To reveal this pathway and underlying photochemical mechanisms, we carried out a combination of quantum chemical calculations and molecular dynamics simulations on plant ( Arabidopsis thaliana ) cryptochrome. The results demonstrate that after photoexcitation a radical pair forms, becomes stabilized through proton transfer, and decays back to the protein's resting state on time scales allowing the protein, in principle, to act as a radical pair-based magnetic sensor. We briefly relate our findings on A. thaliana cryptochrome to photoreaction pathways in animal Cryptochromes.
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Exploring the possibilities for radical pair effects in cryptochrome
Plant Signaling and Behavior, 2008Co-Authors: Ilia A. Solov'yov, Danielle E. Chandler, Klaus SchultenAbstract:The ability of some animals to sense magnetic fields has long captured the human imagination. In our recent paper, we explored how radical pair effects in the protein cryptochrome may underlie the magnetic orientation sense of migratory birds. Here we explain our model and discuss its relationship to experimental results on plant Cryptochromes, as well as discuss the next steps in refining our model, and explore alternate but related possibilities for modeling and understanding cryptochrome as a magnetic sensor.
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Magnetic Field Effects in Arabidopsis thaliana Cryptochrome-1
Biophysical Journal, 2007Co-Authors: Ilia A. Solov’yov, Danielle E. Chandler, Klaus SchultenAbstract:Abstract The ability of some animals, most notably migratory birds, to sense magnetic fields is still poorly understood. It has been suggested that this "magnetic sense" may be mediated by the blue light receptor protein cryptochrome, which is known to be localized in the retinas of migratory birds. Cryptochromes are a class of photoreceptor signaling proteins that are found in a wide variety of organisms and that primarily perform regulatory functions, such as the entrainment of circadian rhythm in mammals and the inhibition of hypocotyl growth in plants. Recent experiments have shown that the activity of cryptochrome-1 in Arabidopsis thaliana is enhanced by the presence of a weak external magnetic field, confirming the ability of cryptochrome to mediate magnetic field responses. Cryptochrome's signaling is tied to the photoreduction of an internally bound chromophore, flavin adenine dinucleotide. The spin chemistry of this photoreduction process, which involves electron transfer from a chain of three tryptophans, can be modulated by the presence of a magnetic field in an effect known as the radical-pair mechanism. Here we present and analyze a model of the flavin-adenine-dinucleotide-tryptophan chain system that incorporates realistic hyperfine coupling constants and reaction rate constants. Our calculations show that the radical-pair mechanism in cryptochrome can produce an increase in the protein's signaling activity of ∼10% for magnetic fields on the order of 5G, which is consistent with experimental results. These calculations, in view of the similarity between bird and plant Cryptochromes, provide further support for a cryptochrome-based model of avian magnetoreception.
Margaret Ahmad - One of the best experts on this subject based on the ideXlab platform.
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Cryptochrome: A photoreceptor with the properties of a magnetoreceptor?
Communicative & integrative biology, 2020Co-Authors: Thorsten Ritz, T Yoshii, C Helfrich-foerster, Margaret AhmadAbstract:It was recently discovered that the photoreceptor cryptochrome is involved in mediating magnetosensitive entrainment of the internal clock of fruit flies.1 This discovery follows other recent studies implicating a role of cryptochrome in mediating magnetic sensitivity in orientation responses of fruit flies2,3 and growth responses of plants.4 Such widespread use of the same molecule for mediating magnetic sensitivity might suggest that cryptochrome is in some way optimal for detecting the magnetic field of the earth and that the magnetoreception function cannot be easily taken over by other molecules. This raises the question what properties might set Cryptochromes apart from other molecules in terms of their ability to detect the geomagnetic field. Here, we will discuss possible answers to this question. We will first review the likely biophysical mechanism by which magnetic fields can be detected by a photoreceptor and discuss what constitutes an optimal photo-magneto-receptor. We will then discuss in how far cryptochrome matches the profile of an optimal molecule and what further steps are required for more conclusive answers.
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photocycle and signaling mechanisms of plant Cryptochromes
Current Opinion in Plant Biology, 2016Co-Authors: Margaret AhmadAbstract:Cryptochromes are flavoprotein blue light receptors that control many aspects of plant growth and development including seedling de-etiolation, elongation growth, the initiation of flowering, and entrainment of the circadian clock. Photon absorption by Arabidopsis Cryptochromes cry1 and cry2 initiates electron transfer to the oxidized flavin cofactor (FADox) and formation of the presumed biological signaling state FADH°. Current literature on the nature and formation of the signaling state is reviewed, and potential novel roles for Cryptochromes in oxidative stress and as magnetosensors are discussed in light of the cryptochrome photocycle.
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Cellular metabolites modulate in vivo signaling of Arabidopsis cryptochrome-1
Plant Signaling & Behavior, 2015Co-Authors: Mohamed A. El-esawi, Thorsten Ritz, Austin Glascoe, Dorothy Engle, Justin Link, Margaret AhmadAbstract:Cryptochromes are blue-light absorbing flavoproteins with multiple signaling roles. In plants, cryptochrome (cry1, cry2) biological activity has been linked to flavin photoreduction via an electron transport chain to the protein surface comprising 3 evolutionarily conserved tryptophan residues known as the ‘Trp triad.’ Mutation of any of the Trp triad residues abolishes photoreduction in isolated cryptochrome protein in vitro and therefore had been suggested as essential for electron transfer to the flavin. However, photoreduction of the flavin in Arabidopsis cry2 proteins occurs in vivo even with mutations in the Trp triad, indicating the existence of alternative electron transfer pathways to the flavin. These pathways are potentiated by metabolites in the intracellular environment including ATP, ADP, AMP, and NADH. In the present work we extend these observations to Arabidopsis cryptochrome 1 and demonstrate that Trp triad substitution mutants at W400F and W324F positions which are not photoreduced in v...
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the Cryptochromes blue light photoreceptors in plants and animals
Annual Review of Plant Biology, 2011Co-Authors: Inês Chaves, Alfred Batschauer, Nathalie Hoang, Thorsten Ritz, Gijsbertus T. J. Van Der Horst, Richard Pokorny, Larsoliver Essen, Klaus Brettel, Martin Byrdin, Margaret AhmadAbstract:Cryptochromes are flavoprotein photoreceptors first identified in Arabidopsis thaliana, where they play key roles in growth and development. Subsequently identified in prokaryotes, archaea, and many eukaryotes, Cryptochromes function in the animal circadian clock and are proposed as magnetoreceptors in migratory birds. Cryptochromes are closely structurally related to photolyases, evolutionarily ancient flavoproteins that catalyze light-dependent DNA repair. Here, we review the structural, photochemical, and molecular properties of cry-DASH, plant, and animal Cryptochromes in relation to biological signaling mechanisms and uncover common features that may contribute to better understanding the function of Cryptochromes in diverse systems including in man.
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human and drosophila Cryptochromes are light activated by flavin photoreduction in living cells
PLOS Biology, 2008Co-Authors: Nathalie Hoang, Erik Schleicher, Sylwia Kacprzak, Jeanpierre Bouly, Marie Picot, William Wu, Albrecht Berndt, Eva Wolf, Robert Bittl, Margaret AhmadAbstract:Cryptochromes are a class of flavoprotein blue-light signaling receptors found in plants, animals, and humans that control plant development and the entrainment of circadian rhythms. In plant Cryptochromes, light activation is proposed to result from photoreduction of a protein-bound flavin chromophore through intramolecular electron transfer. However, although similar in structure to plant Cryptochromes, the light-response mechanism of animal Cryptochromes remains entirely unknown. To complicate matters further, there is currently a debate on whether mammalian Cryptochromes respond to light at all or are instead activated by non–light-dependent mechanisms. To resolve these questions, we have expressed both human and Drosophila cryptochrome proteins to high levels in living Sf21 insect cells using a baculovirus-derived expression system. Intact cells are irradiated with blue light, and the resulting cryptochrome photoconversion is monitored by fluorescence and electron paramagnetic resonance spectroscopic techniques. We demonstrate that light induces a change in the redox state of flavin bound to the receptor in both human and Drosophila Cryptochromes. Photoreduction from oxidized flavin and subsequent accumulation of a semiquinone intermediate signaling state occurs by a conserved mechanism that has been previously identified for plant Cryptochromes. These results provide the first evidence of how animal-type Cryptochromes are activated by light in living cells. Furthermore, human cryptochrome is also shown to undergo this light response. Therefore, human Cryptochromes in exposed peripheral and/or visual tissues may have novel light-sensing roles that remain to be elucidated.
Qin Wang - One of the best experts on this subject based on the ideXlab platform.
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Mechanisms of Cryptochrome-Mediated Photoresponses in Plants
Annual Review of Plant Biology, 2020Co-Authors: Qin WangAbstract:Cryptochromes are blue-light receptors that mediate photoresponses in plants. The genomes of most land plants encode two clades of Cryptochromes, CRY1 and CRY2, which mediate distinct and overlappi...
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the universally conserved residues are not universally required for stable protein expression or functions of Cryptochromes
Molecular Biology and Evolution, 2020Co-Authors: Wenjin He, Tiantian Su, Qin WangAbstract:Universally conserved residues (UCRs) are invariable amino acids evolutionarily conserved among members of a protein family across diverse kingdoms of life. UCRs are considered important for stability and/or function of protein families, but it has not been experimentally examined systematically. Cryptochromes are photoreceptors in plants or light-independent components of the circadian clocks in mammals. We experimentally analyzed 51 UCRs of Arabidopsis cryptochrome 2 (CRY2) that are universally conserved in eukaryotic Cryptochromes from Arabidopsis to human. Surprisingly, we found that UCRs required for stable protein expression of CRY2 in plants are not similarly required for stable protein expression of human hCRY1 in human cells. Moreover, 74% of the stably expressed CRY2 proteins mutated in UCRs retained wild-type-like activities for at least one photoresponses analyzed. Our finding suggests that the evolutionary mechanisms underlying conservation of UCRs or that distinguish UCRs from non-UCRs determining the same functions of individual Cryptochromes remain to be investigated.
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photooligomerization determines photosensitivity and photoreactivity of plant Cryptochromes
Molecular Plant, 2020Co-Authors: Tiantian Su, Xu Wang, Wenjin He, Yadi Chen, Xiaohua Hu, Haoyue Lu, Ying Huang, Qin WangAbstract:Abstract Plant and non-plant species possess cryptochrome (CRY) photoreceptors to mediate blue-light regulation of development or the circadian clock. The blue light-dependent homooligomerization of Arabidopsis CRY2 is a known early photoreaction necessary for its functions, but the photobiochemistry and function of light-dependent homooligomerization and heterooligomerization of Cryptochromes, collectively referred to as CRY photooligomerization, have not been well-established. Here we show that photooligomerization is an evolutionarily conserved photoreaction characteristic of the CRY photoreceptors in plant and some non-plant species. Our analyses of the kinetics of the forward and reverse reactions of photooligomerization of Arabidopsis CRY1 and CRY2 provide a previously unrecognized mechanism underlying the different photosensitivity and photoreactivity of these two closely related photoreceptors. We found that photooligomerization is necessary but not sufficient for the functions of CRY2, implying that CRY photooligomerization must accompany with additional function-empowering conformational changes. We further demonstrate that the CRY2-CRY1 heterooligomerization plays roles in regulating functions of Arabidopsis CRYs in vivo. These results are consistent with the hypothesis that photooligomerization is an evolutionary conserved mechanism that determines the photosensitivity and photoreactivity of plant CRYs.
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beyond the photocycle how Cryptochromes regulate photoresponses in plants
Current Opinion in Plant Biology, 2018Co-Authors: Xu Wang, Qin Wang, Lianfeng GuAbstract:Cryptochromes (CRYs) are blue light receptors that mediate light regulation of plant growth and development. Land plants possess various numbers of Cryptochromes, CRY1 and CRY2, which serve overlapping and partially redundant functions in different plant species. Cryptochromes exist as physiologically inactive monomers in darkness; photoexcited Cryptochromes undergo homodimerization to increase their affinity to the CRY-signaling proteins, such as CIBs (CRY2-interacting bHLH), PIFs (Phytochrome-Interacting Factors), AUX/IAA (Auxin/INDOLE-3-ACETIC ACID), and the COP1-SPAs (Constitutive Photomorphogenesis 1-Suppressors of Phytochrome A) complexes. These light-dependent protein–protein interactions alter the activity of the CRY-signaling proteins to change gene expression and developmental programs in response to light. In the meantime, photoexcitation also changes the affinity of Cryptochromes to the CRY-regulatory proteins, such as BICs (Blue-light Inhibitors of CRYs) and PPKs (Photoregulatory Protein Kinases), to modulate the activity, modification, or abundance of Cryptochromes and photosensitivity of plants in response to the changing light environment.
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New insights into the mechanisms of phytochrome–cryptochrome coaction
New Phytologist, 2017Co-Authors: Qin Wang, Xu WangAbstract:Contents Summary 547 I. Introduction 547 II. Phytochromes mediate light-induced transcription of BICs to inactivate Cryptochromes 548 III. PPKs phosphorylate light-signaling proteins and histones to affect plant development 548 IV. Prospect 550 Acknowledgements 550 References 550 SUMMARY: Plants perceive and respond to light signals by multiple sensory photoreceptors, including phytochromes and Cryptochromes, which absorb different wavelengths of light to regulate genome expression and plant development. Photophysiological analyses have long revealed the coordinated actions of different photoreceptors, a phenomenon referred to as the photoreceptor coaction. The mechanistic explanations of photoreceptor coactions are not fully understood. The function of direct protein-protein interaction of phytochromes and Cryptochromes and common signaling molecules of these photoreceptors, such as SPA1/COP1 E3 ubiquitin ligase complex and bHLH transcription factors PIFs, would partially explain phytochrome-cryptochrome coactions. In addition, newly discovered proteins that block cryptochrome photodimerization or catalyze cryptochrome phosphorylation may also participate in the phytochrome and cryptochrome coaction. This Tansley insight, which is not intended to make a comprehensive review of the studies of photoreceptor coactions, attempts to highlight those recent findings and their possible roles in the photoreceptor coaction.
Carrie L. Partch - One of the best experts on this subject based on the ideXlab platform.
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animal Cryptochromes divergent roles in light perception circadian timekeeping and beyond
Photochemistry and Photobiology, 2017Co-Authors: Alicia K Michael, Carrie L. Partch, Russell N. Van Gelder, Jennifer L FribourghAbstract:Cryptochromes are evolutionarily related to the light-dependent DNA repair enzyme photolyase, serving as major regulators of circadian rhythms in insects and vertebrate animals. There are two types of Cryptochromes in the animal kingdom: Drosophila-like CRYs that act as non-visual photopigments linking circadian rhythms to the environmental light/dark cycle, and vertebrate-like CRYs that do not appear to sense light directly, but control the generation of circadian rhythms by acting as transcriptional repressors. Some animals have both types of CRYs, while others possess only one. Cryptochromes have two domains, the photolyase homology region (PHR) and an extended, intrinsically disordered C-terminus. While all animal CRYs share a high degree of sequence and structural homology in their PHR domains, the C-termini are divergent in both length and sequence identity. Recently, cryptochrome function has been shown to extend beyond its pivotal role in circadian clocks, participating in regulation of the DNA damage response, cancer progression, and glucocorticoid signaling, as well as being implicated as possible magnetoreceptors. In this review, we provide a historical perspective on the discovery of animal Cryptochromes, examine similarities and differences of the two types of animal Cryptochromes, and explore some of the divergent roles for this class of proteins. This article is protected by copyright. All rights reserved.
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Photochemistry and photobiology of cryptochrome blue-light photopigments : The search for a photocycle
Photochemistry and Photobiology, 2005Co-Authors: Carrie L. Partch, Aziz SancarAbstract:Cryptochromes are flavoproteins that exhibit high sequence and structural similarity to the light-dependent DNA-repair enzyme, photolyase. Cryptochromes have lost the ability to repair DNA; instead, they use the energy from near-UV/blue light to regulate a variety of growth and adaptive processes in organisms ranging from bacteria to humans. The photocycle of cryptochrome is not yet known, although it is hypothesized that it may share some similarity to that of photolyase, which utilizes light-driven electron transfer from the catalytic flavin chromophore. In this review, we present genetic evidence for the photoreceptive role of Cryptochromes and discuss recent biochemical studies that have furthered our understanding of the cryptochrome photocycle. In particular, the role of the unique C-terminal domain in cryptochrome phototransduction is discussed.
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Cryptochromes and circadian photoreception in animals
Methods in Enzymology, 2005Co-Authors: Carrie L. Partch, Aziz SancarAbstract:Cryptochromes are flavin- and folate-containing blue-light photoreceptors with a high degree of similarity to DNA photolyase, which repairs ultraviolet-induced DNA damage using blue light to initiate the repair reaction. Cryptochromes play essential roles in the maintenance of circadian rhythms in mice and Drosophila, and genetic data indicate that Cryptochromes function as circadian photoreceptors in these and other animals. However, the photochemical reactions carried out by Cryptochromes are not known at present.
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further evidence for the role of Cryptochromes in retinohypothalamic photoreception phototransduction
Molecular Brain Research, 2004Co-Authors: Carol L Thompson, Carrie L. Partch, Christopher P Selby, David T Plante, Randy J Thresher, Francisco Araujo, Aziz SancarAbstract:Cryptochrome is a blue-light absorbing photopigment that has been proposed to act as a photoreceptor for a variety of nonvisual light-responsive tasks. While mouse models have suggested an important role for cryptochrome in nonvisual photoreception, there are no biochemical data demonstrating the functional photoreceptive capability of cryptochrome in mice. There are two models that describe the effect of cryptochrome on light responsive events: (1) cryptochrome is a photoreceptor or (2) cryptochrome is required for either normal phototransduction from the retina to the brain or for normal transcriptional regulation in the brain, irrespective of light. To differentiate between these two models, we have examined the integrity of the regulatory mechanism of c-fos in cryptochromeless cell lines and in the suprachiasmatic nucleus (SCN) of cryptochromeless mice. Photoinduction of c-fos mRNA in the SCN can be used as a marker for circadian photoreception/phototransduction and it is drastically reduced in mice lacking Cryptochromes. Our results indicate that light-independent transcription regulatory system of c-fos is normal in cryptochromeless mice and that the reduced c-fos light responsiveness in the absence of Cryptochromes is due to a loss of photoreceptor function.
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Further evidence for the role of Cryptochromes in retinohypothalamic photoreception/phototransduction
Molecular Brain Research, 2004Co-Authors: Carol L Thompson, Carrie L. Partch, Christopher P Selby, David T Plante, Randy J Thresher, Francisco Araujo, Aziz SancarAbstract:Cryptochrome is a blue-light absorbing photopigment that has been proposed to act as a photoreceptor for a variety of nonvisual light-responsive tasks. While mouse models have suggested an important role for cryptochrome in nonvisual photoreception, there are no biochemical data demonstrating the functional photoreceptive capability of cryptochrome in mice. There are two models that describe the effect of cryptochrome on light responsive events: (1) cryptochrome is a photoreceptor or (2) cryptochrome is required for either normal phototransduction from the retina to the brain or for normal transcriptional regulation in the brain, irrespective of light. To differentiate between these two models, we have examined the integrity of the regulatory mechanism of c-fos in cryptochromeless cell lines and in the suprachiasmatic nucleus (SCN) of cryptochromeless mice. Photoinduction of c-fos mRNA in the SCN can be used as a marker for circadian photoreception/phototransduction and it is drastically reduced in mice lacking Cryptochromes. Our results indicate that light-independent transcription regulatory system of c-fos is normal in cryptochromeless mice and that the reduced c-fos light responsiveness in the absence of Cryptochromes is due to a loss of photoreceptor function.