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1.
Biochemistry (Mosc) ; 85(Suppl 1): S131-S153, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32087057

ABSTRACT

Proteins of the cryptochrome/DNA photolyase family (CPF) are phylogenetically related and structurally conserved flavoproteins that perform various functions. DNA photolyases repair DNA damage caused by UV-B radiation by exposure to UV-A/blue light simultaneously or subsequently. Cryptochromes are photoreceptor proteins regulating circadian clock, morphogenesis, phototaxis, and other responses to UV and blue light in various organisms. The review describes the structure and functions of CPF proteins, their evolutionary relationship, and possible functions of the CPF ancestor protein.


Subject(s)
Cryptochromes/chemistry , Cryptochromes/physiology , Deoxyribodipyrimidine Photo-Lyase/chemistry , Deoxyribodipyrimidine Photo-Lyase/physiology , Evolution, Molecular , Animals , Circadian Clocks , Cryptochromes/classification , DNA Damage/radiation effects , DNA Repair , DNA-Binding Proteins , Deoxyribodipyrimidine Photo-Lyase/classification , Humans , Phylogeny , Protein Conformation, alpha-Helical , Ultraviolet Rays
2.
J Plant Physiol ; 217: 27-37, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28756992

ABSTRACT

Blue-light reception plays a pivotal role for algae to adapt to changing environmental conditions. In this review we summarize the current structural and mechanistic knowledge about flavin-dependent algal photoreceptors. We especially focus on the cryptochrome and aureochrome type photoreceptors in the context of their evolutionary divergence. Despite similar photochemical characteristics to orthologous photoreceptors from higher plants and animals the algal blue-light photoreceptors have developed a set of unique structural and mechanistic features that are summarized below.


Subject(s)
Cryptochromes/physiology , Diatoms/physiology , Photoreceptors, Plant/physiology , Biological Evolution , Cryptochromes/chemistry , Deoxyribodipyrimidine Photo-Lyase/chemistry , Deoxyribodipyrimidine Photo-Lyase/metabolism , Deoxyribodipyrimidine Photo-Lyase/physiology , Diatoms/metabolism , Molecular Structure , Photoreceptors, Plant/chemistry
3.
J Plant Physiol ; 217: 15-19, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28720252

ABSTRACT

The cryptochrome - photolyase family (CPF) consists of homologous flavoproteins having completely different functions involving DNA repair, circadian rhythm and/or photoreception. From the original photolyases, working either as (6-4) or cyclobutane pyrimidine dimer photolyases, the animal- and plant-type cryptochromes, respectively, evolved and also the more intermediate DASH cryptochromes. Whereas animal cryptochromes work mostly in clock-related functions, plant cryptochromes are also directly involved in developmental processes such as hypocotyl elongation or flower induction. In diatoms, all types of cryptochromes and photolyases were predicted from genome sequences. However, up to now only two proteins have been characterised in more detail, CPF1 and CryP. CPF1 is related to animal-type cryptochromes, but works as a (6-4) photolyase in addition to having photoreceptor functions. It was shown to interact with the CLOCK:Bmal1 heterodimer in a heterologous system, and thus is probably involved in clock-related processes. Moreover, CPF1 directly influences transcription. The latter was also true for CryP, which is a cryptochrome distantly related to plant-type cryptochromes. In addition, CryP influences light-harvesting protein accumulation. For all diatom cryptochromes, down-stream signalling has to proceed via interaction partners different from the classical proteins involved in cryptochrome signalling in higher plants, because these candidates are missing in diatoms.


Subject(s)
Cryptochromes/metabolism , Deoxyribodipyrimidine Photo-Lyase/metabolism , Diatoms/metabolism , Circadian Rhythm , Cryptochromes/physiology , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/physiology , Diatoms/physiology , Phylogeny
4.
J Drugs Dermatol ; 16(5): 61-66, 2017 05 01.
Article in English | MEDLINE | ID: mdl-28628693

ABSTRACT

The limitations of photoprotection modalities have been the inability to arrest the progression of photodamage. Chemoprevention strategies involving a sunscreen has been incomplete because of the need to induce sustained repair of mutations and slow carcinogenesis. Photolyases, or photoreactivation enzymes, serve the role of repairing mutations and damage to DNA induced by ultraviolet (UV) radiation and therefore influence the initiation phases of carcinogenesis. As these enzymes are absent in humans, exogenous forms have been manufactured and are now utilized in topical agents to supplement and augment the innate repair mechanisms that are mostly inefficient. J Drugs Dermatol. 2017;16(5 Suppl):61-66.


Subject(s)
Deoxyribodipyrimidine Photo-Lyase/physiology , Skin Neoplasms/prevention & control , Sunscreening Agents/administration & dosage , Ultraviolet Rays/adverse effects , Animals , DNA Damage/drug effects , DNA Damage/physiology , Deoxyribodipyrimidine Photo-Lyase/antagonists & inhibitors , Humans , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Sunscreening Agents/chemistry
5.
Mutat Res ; 773: 37-42, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25769185

ABSTRACT

Bacteria living in the Antarctic region have developed several adaptive features for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well adapted to high levels of solar UV radiation. A putative photolyase was identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of 579 amino acids with clear photolyase signatures belonging to class II CPD-photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii (68%). Real-time PCR was performed to investigate the potential DNA damage and responses following UVB exposure. CPD photolyase mRNA expression level increased over 50-fold in response to UVB radiation for 6h. Using photolyase complementation assay, we demonstrated that DNA photolyase increased photo-repair more than 116-fold in Escherichia coli strain SY2 under 100µw/cm(2) UVB radiation. To determine whether photolyase is active in vitro, CPD photolyase was over-expressed. It was shown that pyrimidine dimers were split by the action of PHR2. This study reports the unique structure and high activity of the enzyme. These findings are relevant for further understanding of molecular mechanisms of photo-reactivation, and will accelerate the utilization of photolyase in the medical field.


Subject(s)
DNA Repair , Deoxyribodipyrimidine Photo-Lyase/physiology , Microalgae/enzymology , Pyrimidine Dimers/metabolism , Amino Acid Sequence , Deoxyribodipyrimidine Photo-Lyase/genetics , Molecular Sequence Data , Real-Time Polymerase Chain Reaction , Ultraviolet Rays
6.
Cold Spring Harb Perspect Biol ; 5(1): a012575, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23284047

ABSTRACT

Endogenous and exogenous factors constantly challenge cellular DNA, generating cytotoxic and/or mutagenic DNA adducts. As a result, organisms have evolved different mechanisms to defend against the deleterious effects of DNA damage. Among these diverse repair pathways, direct DNA-repair systems provide cells with simple yet efficient solutions to reverse covalent DNA adducts. In this review, we focus on recent advances in the field of direct DNA repair, namely, photolyase-, alkyltransferase-, and dioxygenase-mediated repair processes. We present specific examples to describe new findings of known enzymes and appealing discoveries of new proteins. At the end of this article, we also briefly discuss the influence of direct DNA repair on other fields of biology and its implication on the discovery of new biology.


Subject(s)
DNA Damage , DNA Repair/physiology , Alkyl and Aryl Transferases/metabolism , Alkyl and Aryl Transferases/physiology , Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Cryptochromes/metabolism , Cryptochromes/physiology , DNA Repair Enzymes/metabolism , DNA Repair Enzymes/physiology , Deoxyribodipyrimidine Photo-Lyase/metabolism , Deoxyribodipyrimidine Photo-Lyase/physiology , Dioxygenases/metabolism , Dioxygenases/physiology , Humans , Methylation , Models, Genetic , Obesity/genetics , Proteins/genetics , RNA/chemistry , RNA/metabolism
7.
J Biol Rhythms ; 27(1): 3-11, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22306969

ABSTRACT

Cryptochromes and photolyases belong to the same family of flavoproteins but, despite being structurally conserved, display distinct functions. Photolyases use visible light to repair ultraviolet-induced DNA damage. Cryptochromes, however, function as blue-light receptors, circadian photoreceptors, or repressors of the CLOCK/BMAL1 heterodimer, the transcription activator controlling the molecular circadian clock. Here, we present evidence that the functional divergence between cryptochromes and photolyases is not so univocal. Chrysodeixis chalcites nucleopolyhedrovirus possesses 2 photolyase-like genes: phr1 and phr2. We show that PHR1 and PHR2 are able to bind the CLOCK protein. Only for PHR2, however, the physical interaction with CLOCK represses CLOCK/BMAL1-driven transcription. This result shows that binding of photolyase per se is not sufficient to inhibit the CLOCK/BMAL1 heterodimer. PHR2, furthermore, affects the oscillation of immortalized mouse embryonic fibroblasts, suggesting that PHR2 can regulate the molecular circadian clock. These findings are relevant for further understanding the evolution of cryptochromes and photolyases as well as behavioral changes induced in insects by baculoviruses.


Subject(s)
CLOCK Proteins/metabolism , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/physiology , Nucleopolyhedroviruses/enzymology , ARNTL Transcription Factors/antagonists & inhibitors , Animals , Circadian Clocks/drug effects , HEK293 Cells , Humans , Mice , NIH 3T3 Cells , Transcription, Genetic/drug effects
8.
Annu Rev Plant Biol ; 62: 335-64, 2011.
Article in English | MEDLINE | ID: mdl-21526969

ABSTRACT

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.


Subject(s)
Cryptochromes/physiology , Light Signal Transduction , Plants/metabolism , Adenosine Triphosphate/metabolism , Animals , Cryptochromes/chemistry , Cryptochromes/classification , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/chemistry , Deoxyribodipyrimidine Photo-Lyase/classification , Deoxyribodipyrimidine Photo-Lyase/physiology , Homing Behavior , Insecta/physiology , Magnetics , Mice , Oxidation-Reduction , Phosphorylation/physiology
9.
J Gen Virol ; 91(Pt 4): 907-14, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19955559

ABSTRACT

Cyclobutane pyrimidine dimer (CPD) photolyases convert UV-induced CPDs in DNA into monomers using visible light as the energy source. Two phr genes encoding class II CPD photolyases PHR1 and PHR2 have been identified in Chrysodeixis chalcites nucleopolyhedrovirus (ChchNPV). Transient expression assays in insect cells showed that PHR1-EGFP fusion protein was localized in the nucleus. Early after transfection, PHR2-EGFP was distributed over the cytoplasm and nucleus but, over time, it became localized predominantly in the nucleus. Immunofluorescence analysis with anti-PHR2 antiserum showed that, early after transfection, non-fused PHR2 was already present mainly in the nucleus, suggesting that the fusion of PHR2 to EGFP hindered its nuclear import. Both PHR-EGFP fusion proteins strongly colocalized with chromosomes and spindle, aster and midbody structures during host-cell mitosis. When PHR2-EGFP-transfected cells were superinfected with Autographa californica multiple-nucleocapsid NPV (AcMNPV), the protein colocalized with virogenic stroma, the replication factories of baculovirus DNA. The collective data support the supposition that the PHR2 protein plays a role in baculovirus DNA repair.


Subject(s)
Cell Nucleus/enzymology , Chromosomes/enzymology , Deoxyribodipyrimidine Photo-Lyase/analysis , Moths/virology , Nucleopolyhedroviruses/enzymology , Spindle Apparatus/enzymology , Animals , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/physiology , Fluorescent Antibody Technique , Mitosis , Transfection
10.
J Exp Biol ; 212(17): 2760-6, 2009 Sep 01.
Article in English | MEDLINE | ID: mdl-19684208

ABSTRACT

The larvae of most coral species spend some time in the plankton, floating just below the surface and hence exposed to high levels of ultraviolet radiation (UVR). The high levels of UVR are potentially stressful and damaging to DNA and other cellular components, such as proteins, reducing survivorship. Consequently, mechanisms to either shade (prevent) or repair damage potentially play an important role. In this study, the role of photoreactivation in the survival of coral planulae was examined. Photoreactivation is a light-stimulated response to UV-damaged DNA in which photolyase proteins repair damaged DNA. Photoreactivation rates, as well as the localization of photolyase, were explored in planulae under conditions where photoreactivation was or was not inhibited. The results indicate that photoreactivation is the main DNA repair pathway in coral planulae, repairing UV-induced DNA damage swiftly (K=1.75 h(-1) and a half-life of repair of 23 min), with no evidence of any light-independent DNA repair mechanisms, such as nucleotide excision repair (NER), at work. Photolyase mRNA was localized to both the ectoderm and endoderm of the larvae. The amount of cell death in the coral planulae increased significantly when photoreactivation was inhibited, by blocking photoreactivating light. We found that photoreactivation, along with additional UV shielding in the form of five mycosporine-like amino acids, are sufficient for survival in surface tropical waters and that planulae do not accumulate DNA damage despite being exposed to high UVR.


Subject(s)
Anthozoa/genetics , DNA Damage , DNA Repair/physiology , Ultraviolet Rays , Animals , Anthozoa/enzymology , Anthozoa/radiation effects , Apoptosis/radiation effects , Deoxyribodipyrimidine Photo-Lyase/antagonists & inhibitors , Deoxyribodipyrimidine Photo-Lyase/metabolism , Deoxyribodipyrimidine Photo-Lyase/physiology , Larva/enzymology , Larva/genetics , Larva/radiation effects , RNA, Messenger/metabolism
11.
FEBS J ; 276(16): 4290-303, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19624734

ABSTRACT

Exploring enzymatic mechanisms at a molecular level is one of the major challenges in modern biophysics. Based on enzyme structure data, as obtained by X-ray crystallography or NMR spectroscopy, one can suggest how substrates and products bind for catalysis. However, from the 3D structure alone it is very rarely possible to identify how intermediates are formed and how they are interconverted. Molecular spectroscopy can provide such information and thus supplement our knowledge on the specific enzymatic reaction under consideration. In the case of enzymatic processes in which paramagnetic molecules play a role, EPR and related methods such as electron-nuclear double resonance (ENDOR) are powerful techniques to unravel important details, e.g. the electronic structure or the protonation state of the intermediate(s) carrying (the) unpaired electron spin(s). Here, we review recent EPR/ENDOR studies of blue-light active flavoproteins with emphasis on photolyases that catalyze the enzymatic repair of UV damaged DNA, and on cryptochrome blue-light photoreceptors that act in several species as central components of the circadian clock.


Subject(s)
Electron Spin Resonance Spectroscopy/methods , Flavoproteins/chemistry , Flavoproteins/physiology , Circadian Rhythm , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/chemistry , Deoxyribodipyrimidine Photo-Lyase/physiology , Light
14.
Mol Biol Cell ; 19(8): 3254-62, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18495868

ABSTRACT

Cryptochromes are blue-light receptors that have presumably evolved from the DNA photolyase protein family, and the genomes of many organisms contain genes for both types of molecules. Both protein structures resemble each other, which suggests that light control and light protection share a common ancient origin. In the genome of the filamentous fungus Aspergillus nidulans, however, only one cryptochrome/photolyase-encoding gene, termed cryA, was identified. Deletion of the cryA gene triggers sexual differentiation under inappropriate culture conditions and results in up-regulation of transcripts encoding regulators of fruiting body formation. CryA is a protein whose N- and C-terminal synthetic green fluorescent protein fusions localize to the nucleus. CryA represses sexual development under UVA (350-370 nm) light both on plates and in submerged culture. Strikingly, CryA exhibits photorepair activity as demonstrated by heterologous complementation of a DNA repair-deficient Escherichia coli strain as well as overexpression in an A. nidulans uvsBDelta genetic background. This is in contrast to the single deletion cryADelta strain, which does not show increased sensitivity toward UV-induced damage. In A. nidulans, cryA encodes a novel type of cryptochrome/photolyase that exhibits a regulatory function during light-dependent development and DNA repair activity. This represents a paradigm for the evolutionary transition between photolyases and cryptochromes.


Subject(s)
Aspergillus nidulans/metabolism , Deoxyribodipyrimidine Photo-Lyase/physiology , Flavoproteins/metabolism , Gene Expression Regulation, Fungal , Amino Acid Sequence , Cryptochromes , DNA Damage , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/metabolism , Gene Deletion , Green Fluorescent Proteins/metabolism , Light , Models, Biological , Molecular Sequence Data , Phylogeny , Protein Structure, Tertiary , Reproduction , Sequence Homology, Amino Acid
15.
Cell Res ; 18(1): 3-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18157159

ABSTRACT

The history of the repair of damaged DNA can be traced to the mid-1930s. Since then multiple DNA repair mechanisms, as well as other biological responses to DNA damage, have been discovered and their regulation has been studied. This article briefly recounts the early history of this field.


Subject(s)
DNA Repair/physiology , Animals , DNA Damage/physiology , DNA Repair/genetics , Deoxyribodipyrimidine Photo-Lyase/physiology , Genetic Predisposition to Disease , Humans , Mutagenesis/genetics , Neoplasms/genetics
16.
J Phys Chem B ; 111(40): 11843-9, 2007 Oct 11.
Article in English | MEDLINE | ID: mdl-17867670

ABSTRACT

Exposure of two adjacent thymines in DNA to UV light of 260-320 nm can result in the formation of the cis,syn-cyclobutane pyrimidine dimer (CPD). The structure of DNA containing an intrahelical CPD lesion has been previously studied experimentally and computationally. However, the structure of the extrahelical, flipped-out, CPD lesion, which has been shown to be the structure that binds to the CPD repair enzyme, DNA photolyase, has yet to be reported. In this work the structure of both the flipped-in and the flipped-out CPD lesions in duplex DNA is reported. These structures were calculated using 8 ns molecular dynamics (MD) simulations. These structures are then used to define the starting and ending points for the base-flipping process for the CPD lesion. Using a complex, two-dimensional pseudodihedral coordinate, the potential of mean force (PMF) for the base-flipping process was calculcated using novel methodology. The free energy of the flipped-out CPD is roughly 6.5 kcal/mol higher than that of the flipped-in state, indicating that the barrier to flipping out is much lower for CPD than for undamaged DNA. This may indicate that the flipped-out CPD lesion may be recognized by its repair enzyme, DNA photolyase, whereas previous studies of other damaged, as well as nondamaged, bases indicate that they are recognized by enzymes in the intrahelical, flipped-in state.


Subject(s)
DNA/chemistry , Pyrimidine Dimers/chemistry , Computer Simulation , DNA/metabolism , Deoxyribodipyrimidine Photo-Lyase/physiology , Humans , Models, Chemical , Models, Molecular , Pyrimidine Dimers/metabolism , Synechococcus/enzymology , Thermodynamics
17.
Eukaryot Cell ; 6(9): 1682-92, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17545314

ABSTRACT

The photolyases, DNA repair enzymes that use visible and long-wavelength UV light to repair cyclobutane pyrimidine dimers (CPDs) created by short-wavelength UV, belong to the larger photolyase-cryptochrome gene family. Cryptochromes (UVA-blue light photoreceptors) lack repair activity, and sensory and regulatory roles have been defined for them in plants and animals. Evolutionary considerations indicate that cryptochromes diverged from CPD photolyases before the emergence of eukaryotes. In prokaryotes and lower eukaryotes, some photolyases might have photosensory functions. phr1 codes for a class I CPD photolyase in Trichoderma atroviride. phr1 is rapidly induced by blue and UVA light, and its photoinduction requires functional blue light regulator (BLR) proteins, which are White Collar homologs in Trichoderma. Here we show that deletion of phr1 abolished photoreactivation of UVC (200 to 280 nm)-inhibited spores and thus that PHR1 is the main component of the photorepair system. The 2-kb 5' upstream region of phr1, with putative light-regulated elements, confers blue light regulation on a reporter gene. To assess phr1 photosensory function, fluence response curves of this light-regulated promoter were tested in null mutant (Deltaphr1) strains. Photoinduction of the phr1 promoter in Deltaphr1 strains was >5-fold more sensitive to light than that in the wild type, whereas in PHR1-overexpressing lines the sensitivity to light increased about 2-fold. Our data suggest that PHR1 may regulate its expression in a light-dependent manner, perhaps through negative modulation of the BLR proteins. This is the first evidence for a regulatory role of photolyase, a role usually attributed to cryptochromes.


Subject(s)
Deoxyribodipyrimidine Photo-Lyase/genetics , Fungal Proteins/genetics , Gene Expression Regulation, Fungal , Homeostasis , Trichoderma/enzymology , Amino Acid Sequence , Cryptochromes , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/physiology , Flavoproteins/metabolism , Fungal Proteins/physiology , Gene Deletion , Gene Expression/radiation effects , Green Fluorescent Proteins/analysis , Green Fluorescent Proteins/genetics , Molecular Sequence Data , Promoter Regions, Genetic/radiation effects , Trichoderma/genetics , Trichoderma/radiation effects , Ultraviolet Rays
18.
J Photochem Photobiol B ; 87(2): 137-43, 2007 May 25.
Article in English | MEDLINE | ID: mdl-17383890

ABSTRACT

Ultraviolet light induces photoproducts, cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4PPs), in cellular DNA, which cause cytotoxic and genotoxic effects on the cells. Cells have several DNA repair mechanisms to repair the damage and to maintain genetic information of the cells. Photoreactivation is one of the DNA repair mechanism to remove UV-induced DNA damage from cellular DNA catalyzed by photolyase under visible light. Two types of photolyase, CPD photolyase and (6-4) photolyase, are specific for CPDs and for (6-4)PPs. We have isolated a gene product encoding CPD photolyase, named PHR2, from Dunaliella salina which is a kind of unicellular alga. Sequence analysis showed that PHR2 encodes a protein that has 529 amino acids and is similar to other Class II CPD photolyase. The complementation assay of the photoreactivation deficiency of the Escherichia coli SY2 by PHR2 cDNA showed a significant increase in survival rate when cells were irradiated with UV-C. Real-time PCR analysis indicated that the transcription of PHR2 was induced by UV-C, white light, high salinity, and H(2)O(2).


Subject(s)
Deoxyribodipyrimidine Photo-Lyase/genetics , Pyrimidine Dimers , Algal Proteins/genetics , Algal Proteins/physiology , Amino Acid Sequence , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/physiology , Eukaryota/enzymology , Molecular Sequence Data , Sequence Alignment , Sequence Analysis, Protein , Survival Rate , Ultraviolet Rays/adverse effects
19.
Article in English | MEDLINE | ID: mdl-18419269

ABSTRACT

Cryptochrome (CRY) is a photolyase-like flavoprotein with no DNA-repair activity but with known or presumed blue-light receptor function. Animal CRYs have DNA-binding and autokinase activities, and their flavin cofactor is reduced by photoinduced electron transfer. In Drosophila, CRY is a major circadian photoreceptor, and in mammals, the two CRY proteins are core components of the molecular clock and potential circadian photoreceptors. In mammals, CRYs participate in cell cycle regulation and the cellular response to DNA damage by controlling the expression of some cell cycle genes and by directly interacting with checkpoint proteins.


Subject(s)
Flavoproteins/chemistry , Flavoproteins/physiology , Animals , Cell Cycle , Circadian Rhythm , Cryptochromes , Deoxyribodipyrimidine Photo-Lyase/chemistry , Deoxyribodipyrimidine Photo-Lyase/genetics , Deoxyribodipyrimidine Photo-Lyase/physiology , Drosophila/genetics , Drosophila/physiology , Drosophila Proteins/chemistry , Drosophila Proteins/genetics , Drosophila Proteins/physiology , Evolution, Molecular , Eye Proteins/chemistry , Eye Proteins/genetics , Eye Proteins/physiology , Flavoproteins/genetics , Flavoproteins/history , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Models, Molecular , Molecular Structure , Photochemistry , Photoreceptor Cells, Invertebrate/chemistry , Photoreceptor Cells, Invertebrate/physiology , Photoreceptor Cells, Vertebrate/chemistry , Photoreceptor Cells, Vertebrate/physiology , Phylogeny , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/physiology
20.
Article in English | MEDLINE | ID: mdl-18419270

ABSTRACT

Members of the photolyase/cryptochrome family are flavoproteins that share an extraordinary conserved core structure (photolyase homology region, PHR), but the presence of a carboxy-terminal extension is limited to the cryptochromes. Photolyases are DNA-repair enzymes that remove UV-light-induced lesions. Cryptochromes of plants and Drosophila act as circadian photoreceptors, involved in light entrainment of the biological clock. Using knockout mouse models, mammalian cryptochromes (mCRY1 and mCRY2) were identified as essential components of the clock machinery. Within the mammalian transcription-translation feedback loop generating rhythmic gene expression, mCRYs potently inhibit the transcription activity of the CLOCK/BMAL1 heterodimer and protect mPER2 from 26S-protesome-mediated degradation. By analyzing a set of mutant mCRY1 proteins and photolyase/mCRY1 chimeric proteins, we found that the carboxyl terminus has a determinant role in mCRY1 function by harboring distinguished domains involved in nuclear import and interactions with other clock proteins. Moreover, the carboxyl terminus must cross-talk with the PHR to establish full transcription repression capacity in mCRY1. We propose that the presence of the carboxyl terminus in cryptochromes, which varies in sequence composition among mammalian, Drosophila, and plant CRYs, is critical for their different functions and possibly contributed to shape the different architecture and biochemistry of the clock machineries in these organisms.


Subject(s)
Flavoproteins/chemistry , Flavoproteins/physiology , Animals , Circadian Rhythm/genetics , Circadian Rhythm/physiology , Cryptochromes , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/chemistry , Deoxyribodipyrimidine Photo-Lyase/genetics , Deoxyribodipyrimidine Photo-Lyase/physiology , Dimerization , Flavoproteins/genetics , Light Signal Transduction , Mice , Mice, Knockout , Models, Biological , Phenotype , Transcription, Genetic
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