Structure and Function of Photolyase and in Vivo Enzymology: 50th Anniversary

Sancar, Aziz

doi:10.1074/jbc.r800052200

Cited by 179 publications

(196 citation statements)

References 52 publications

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“…If we don't take into account the so-called CRY-DASH proteins, which turned out to be photolyases specific for pyrimidine dimers in single-stranded DNA (34), the current state of knowledge regarding CRY action mechanism might be summarized as follows: (i) Photolyase, which evolutionarily is related to CRY contains the flavin cofactor in the two-electron reduced and deprotonated FADH − form and carries out catalysis by a nonreductive cyclic electron transfer reaction (9,35). In contrast, the redox state of FAD in CRY is not known with certainty.…”

Section: Discussionmentioning

confidence: 99%

Reaction mechanism of Drosophila cryptochrome

Öztürk

Selby

Annayev

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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122

174

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Cryptochrome (CRY) is a blue-light sensitive flavoprotein that functions as the primary circadian photoreceptor in Drosophila melanogaster. The mechanism by which it transmits the light signal to the core clock circuitry is not known. We conducted in vitro studies on the light-induced conformational change in CRY and its effect on protein-protein interaction and performed in vivo analysis of the lifetime of the signaling state of the protein to gain some insight into the mechanism of phototransduction. We find that exposure of CRY to blue light induces a conformation similar to that of the constitutively active CRY mutant with a C-terminal deletion (CRYΔ). This light-induced conformation has a half-life of ∼15 min in the dark at 25°C and is characterized by increased affinity to Jetlag E3 ligase. In vivo analysis reveals that in the Drosophila S2 cell line, the signaling state induced by a millisecond light exposure has a half-life of 27 min in the dark at 0°C during which period it is susceptible to degradation by the ubiquitin-proteasome system. These findings lead to a plausible model for circadian photoreception/ phototransduction in Drosophila.circadian clock | photocycle | proteolysis | sensory flavoprotein C ryptochrome (CRY) is a flavoprotein that regulates growth and development in plants in response to blue light, functions as a circadian photoreceptor in Drosophila and other insects, and acts as a core component of the molecular clock in mammalian organisms (1-4). Despite extensive research on CRYs photosensory function in Arabidopsis and Drosophila, its mechanism of photoreception/phototransduction is poorly understood. Even the redox status of the FAD cofactor is a matter of some debate (5-8). In the phylogenetically related protein, DNA photolyase, photoinduced cyclic electron transfer from the FADH − cofactor to a pyrimidine photodimer repairs the DNA damage and regenerates the FADH − for new rounds of catalysis (9-11). However, there is no evidence so far for a similar reaction in either Arabidopsis CRY1 (AtCRY1) and CRY2 or Drosophila CRY, which at present are the most extensively studied CRYs. The lack of evidence for a cyclic redox reaction in CRYs has led to consideration of the mechanisms of other photosensory flavoproteins as potential models for CRYs in general and Drosophila CRY in particular.Currently, three types of photosensory flavoproteins are known (12): the photolyase/CRY family, the LOV domain proteins such as phototropin, and the BLUF domain proteins such as the photoactivated adenylyl cyclase. Whereas photolyase, as noted above, carries out catalysis by light-induced cyclic electron transfer, LOV and BLUF domain proteins initiate photosignaling by a lightinduced conformational change. Failing to obtain any evidence for CRY signaling by a photolyase-like mechanism, we considered the possibility that CRY also may carry out its light signaling by a light-induced conformational change that would affect the interaction of CRY with downstream signal transduction partners (13,14). Inde...

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Section: Discussionmentioning

confidence: 99%

Reaction mechanism of Drosophila cryptochrome

Öztürk

Selby

Annayev

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

122

174

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“…Two classes of PHRs have been identified, one specific for CPDs (CPD PHRs) and the other specific for (6-4) photoproducts (64PHRs). 74,75) Both CPD PHRs and 64PHRs are induced by visible light in cultured fish cells. 52,59,76) We have obtained evidence indicating that photoreactivation in zebrafish is a cell-autonomous phenomenon, and that both the induction of 64PHRs in response to light and the subsequent light-dependent repair of DNA by 64PHRs are essential for successful photoreactivation.…”

Section: Light-dependent Circadian Entrainment and Ddr Share A Commonmentioning

confidence: 99%

“…73) Photoreactivation is mediated by DNA photolyases (PHRs), which are DNA repair enzymes. 74 as an energy source. Two classes of PHRs have been identified, one specific for CPDs (CPD PHRs) and the other specific for (6-4) photoproducts (64PHRs).…”

Section: Light-dependent Circadian Entrainment and Ddr Share A Commonmentioning

confidence: 99%

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

Uchida

Hirayama

Nishina

2010

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFrom bacteria to humans, almost all organisms can adapt the timing of their physiology to the cyclic changes of their environment, thanks to a naturally-selected intrinsic timekeeping system called the circadian clock. 1) The circadian clock enhances the physiological efficiency and survival of an organism by organizing its behavior and body functions. 2,3) During the circadian day, the organism's physiology is given over to catabolic processes, whereas the anabolic functions of growth, repair and consolidation occur at night. To achieve this schedule in mammals, the circadian clock regulates a number of physiological functions, including sleep and wakefulness, food intake, body temperature, cardiovascular and renal activity, hormone production, hepatic metabolism and immune responses. 4,5) Accordingly, disruption of the circadian clock in humans has been linked to profound effects on health, including insomnia, stomach ailments, depression and cancer. 4,5) In most organisms, the molecular mechanisms underlying the establishment and maintenance of biological rhythms comprise interconnected transcription-translation feedback loops in which some clock factors repress their own transcription once they have attained critical levels. 2,3) These oscillators have the property of being endogenous and cellautonomous systems that maintain their rhythm in the absence of external time cues. 6) Both vertebrates and invertebrates have circadian oscillators scattered throughout their bodies. 7,8) In mammals, the circadian system is composed of both central and peripheral oscillators. 7) The mammalian central clock is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus of the brain. 9) This central clock acts as a coordinator and provides time signals via both neural and humoral routes that entrain independent peripheral clocks. Dysfunction of the central clock does not inactivate the peripheral clocks but instead causes individual peripheral oscillators to become temporally uncoupled. [10][11][12] To guarantee that an organism's behavior remains tied to the rhythms of its environment, the circadian clock must be able to reset itself in response to environmental cues. 9,13,14) The main environmental stimulus for organisms is light, which is provided in day-night cycles. Mammals have no photoreceptors in peripheral tissues, 15) so that the effect of light on peripheral clocks is indirect. 13) For the mammalian clock, the SCN integrates photic cues from the retina and uses neural and humoral signals to transmit this information to peripheral clocks, synchronizing them. [16][17][18] This communication between the central and peripheral clocks results in the seamless regulation of fundamental physiological functions. 4,8) Interestingly, peripheral clocks can also respond directly to SCN-independent signals such as feeding and temperature change. 19,20) However, the physiological role of SCN-independent responses of peripheral clocks is not yet fully understood. A recent study has reported that ...

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“…(2)]. They have high sequence-homology and structural similarity to their evolutionary ancestors, the DNA photolyases (3,4) and all members of the cryptochrome/photolyase family contain the redox-active cofactor flavin adenine dinucleotide (FAD). Cryptochromes were proposed as potential magnetoreceptors by Ritz et al in 2000 in an attempt to explain the mechanism by which migratory birds are able to sense the direction of the Earth's magnetic field for the purpose of navigation (5).…”

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confidence: 99%

Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor

Maeda

Robinson

Henbest

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

314

480

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Among the biological phenomena that fall within the emerging field of “quantum biology” is the suggestion that magnetically sensitive chemical reactions are responsible for the magnetic compass of migratory birds. It has been proposed that transient radical pairs are formed by photo-induced electron transfer reactions in cryptochrome proteins and that their coherent spin dynamics are influenced by the geomagnetic field leading to changes in the quantum yield of the signaling state of the protein. Despite a variety of supporting evidence, it is still not clear whether cryptochromes have the properties required to respond to magnetic interactions orders of magnitude weaker than the thermal energy, k B T . Here we demonstrate that the kinetics and quantum yields of photo-induced flavin—tryptophan radical pairs in cryptochrome are indeed magnetically sensitive. The mechanistic origin of the magnetic field effect is clarified, its dependence on the strength of the magnetic field measured, and the rates of relevant spin-dependent, spin-independent, and spin-decoherence processes determined. We argue that cryptochrome is fit for purpose as a chemical magnetoreceptor.

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Structure and Function of Photolyase and in Vivo Enzymology: 50th Anniversary

Cited by 179 publications

References 52 publications

Reaction mechanism of Drosophila cryptochrome

Reaction mechanism of Drosophila cryptochrome

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor

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