Browsing by Subject "CRYPTOCHROME"

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  • Toledo, Miriam; Batista-Gonzalez, Ana; Merheb, Emilio; Aoun, Marie Louise; Tarabra, Elena; Feng, Daorong; Sarparanta, Jaakko; Merlo, Paola; Botre, Francesco; Schwartz, Gary J.; Pessin, Jeffrey E.; Singh, Rajat (2018)
    The circadian clock coordinates behavioral and circadian cues with availability and utilization of nutrients. Proteasomal degradation of clock repressors, such as cryptochrome (CRY) 1, maintains periodicity. Whether macroautophagy, a quality control pathway, degrades circadian proteins remains unknown. Here we show that circadian proteins BMAL1, CLOCK, REV-ERB alpha, and CRY1 are lysosomal targets, and that macroautophagy affects the circadian clock by selectively degrading CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that CRY1 degradation is timeimprinted to maintenance of blood glucose. High-fat feeding accelerates autophagic CRY1 degradation and contributes to obesity-associated hyperglycemia. CRY1 contains several light chain 3 (LC3)-interacting region (LIR) motifs, which facilitate the interaction of cargo proteins with the autophagosome marker LC3. Using mutational analyses, we identified two distinct LIRs on CRY1 that exert circadian glycemic control by regulating CRY1 degradation, revealing LIRs as potential targets for controlling hyperglycemia.
  • Merikanto, Ilona; Lahti, Jari; Kuula, Liisa; Heinonen, Kati; Räikkönen, Katri; Andersson, Sture; Strandberg, Timo; Pesonen, Anu-Katriina (2018)
    Objective: Recent genome-wide association studies (GWASs) have revealed new genetic variants behind self-reported individual circadian preference, a distinct biological trait that is fairly stable during adulthood. In this study we analyze whether these genetic variants associate with objectively measured sleep timing from childhood to adolescence, over a nine-year period, with self-reported circadian preference during late adolescence. Methods: The participants (N = 100, 61% girls) came from a community cohort from Finland born in 1998. Sleep midpoint was measured with actigraphy at 8, 12 and 17 years. Circadian preference was self-reported at the age of 17 years. Single nucleotide polymorphisms (SNPs) were extracted at 12 years of age from the Illumina OmniExpress Exome 1.2 bead array data. Weighted polygenic risk scores (PRSs) were calculated based on top SNPs from a recent GWAS for morningness-eveningness in an adult population. Results: The PRS for circadian preference towards morningness was associated with earlier sleep midpoint from childhood to adolescence. When the time points were analyzed separately, the association between genetic tendency towards morning preference and earlier sleep midpoint was strongest among the 17-year-olds. Furthermore, the shift towards later sleep rhythm from early to late adolescence was milder for those with a higher PRS for morning preference. PRS for morning preference was also associated with self-reported circadian preference towards morningness in late adolescence. Conclusion: Our results suggest that genetic variants found for circadian preference in adults are already associated with objective sleep timing during childhood and adolescence, and predict individual developmental sleep trajectories from childhood onwards. (C) 2018 Published by Elsevier B.V.
  • Yan, Yan; Stoddard, Frederick L.; Neugart, Susanne; Sadras, Victor O.; Lindfors, Anders; Morales, Luis Orlando; Aphalo, Pedro J. (2019)
    Blue light and UV radiation shape a plant's morphology and development, but accession-dependent responses under natural conditions are unclear. Here we tested the hypothesis that two faba bean (Vicia faba L.) accessions adapted to different latitudes and altitudes vary in their responses to solar blue and UV light. We measured growth, physiological traits, phenolic profiles and expression of associated genes in a factorial experiment combining two accessions (Aurora, a Swedish cultivar adapted to high latitude and low altitude; ILB938, from the Andean region of Colombia and Ecuador, adapted to low latitude and high altitude) and four filter treatments created with plastic sheets: 1. transparent as control; 2. attenuated short UV (290-350 nm); 3. attenuated UV (290-400 nm); 4. attenuated blue and UV light. In both accessions, the exclusion of blue and UV light increased plant height and leaf area, and decreased transcript abundance of ELONGATED HYPOCOTYL 5 (HY5) and TYROSINE AMINOTRANSFERASE 3 (TAT3). Blue light and short UV induced the accumulation of epidermal and whole-leaf flavonoids, mainly quercetins, and the responses in the two accessions were through different glycosides. Filter treatments did not affect kaempferol concentration, but there were more tri-glycosides in Aurora and di-glycosides in ILB938. Furthermore, fewer quercetin glycosides were identified in ILB938. The transcript abundance was consistently higher in Aurora than in ILB938 for all seven investigated genes: HY5, TAT3, CHALCONE SYNTHASE (CHS), CHALCONE ISOMERASE (CHI), DON-GLUCOSYLTRANSFERASE 1 (DOGT1), ABA INSENSITIVE 2 (ABI2), AUXIN-INDUCIBLE 2-27 (IAA5). The two largest differences in transcript abundance between the two accessions across treatments were 132-fold in CHS and 30-fold in DOGT1 which may explain the accession-dependent glycosylation patterns. Our findings suggest that agronomic selection for adaptation to high altitude may favour phenotypes with particular adaptations to the light environment, including solar UV and blue light.
  • Cellini, Andrea; Wahlgren, Weixiao Yuan; Henry, Leocadie; Pandey, Suraj; Ghosh, Swagatha; Castillon, Leticia; Claesson, Elin; Takala, Heikki; Kubel, Joachim; Nimmrich, Amke; Kuznetsova, Valentyna; Nango, Eriko; Iwata, So; Owada, Shigeki; Stojkovic, Emina A.; Schmidt, Marius; Ihalainen, Janne A.; Westenhoff, Sebastian (2021)
    (6-4) photolyases are flavoproteins that belong to the photolyase/cryptochrome family. Their function is to repair DNA lesions using visible light. Here, crystal structures of Drosophila melanogaster (6-4) photolyase [Dm(6-4)photolyase] at room and cryogenic temperatures are reported. The room-temperature structure was solved to 2.27 angstrom resolution and was obtained by serial femtosecond crystallography (SFX) using an X-ray free-electron laser. The crystallization and preparation conditions are also reported. The cryogenic structure was solved to 1.79 angstrom resolution using conventional X-ray crystallography. The structures agree with each other, indicating that the structural information obtained from crystallography at cryogenic temperature also applies at room temperature. Furthermore, UV-Vis absorption spectroscopy confirms that Dm(6-4)photolyase is photoactive in the crystals, giving a green light to time-resolved SFX studies on the protein, which can reveal the structural mechanism of the photoactivated protein in DNA repair.