The Potorous CPD Photolyase Rescues a Cryptochrome-Deficient Mammalian Circadian Clock
| Autor: | Karl Brand, Monika I. Bajek, Gijsbertus T. J. van der Horst, Kazuhiro Yagita, M.A. Biernat, André P.M. Eker, António Carvalho da Silva, Romana M. Nijman, Inês Chaves, Shoko Saito |
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| Přispěvatelé: | Molecular Genetics, Cell biology |
| Rok vydání: | 2011 |
| Předmět: |
Anatomy and Physiology
Mouse Circadian clock Laboratory of Virology CLOCK Proteins lcsh:Medicine Mice 0302 clinical medicine Cryptochrome Gene Duplication Chlorocebus aethiops Molecular Cell Biology dna photolyase Luciferases lcsh:Science Cells Cultured Mice Knockout Genetics 0303 health sciences Multidisciplinary ARNTL Transcription Factors Reverse Transcriptase Polymerase Chain Reaction Animal Models PE&RC peripheral clock Liver light photoreceptor family COS Cells transcription Deoxyribodipyrimidine Photo-Lyase Protein Binding Research Article DNA repair Immunoblotting Mice Transgenic biological clock Biology Transfection skin-cancer Molecular Genetics Laboratorium voor Virologie 03 medical and health sciences Model Organisms Potoroidae Circadian Clocks evolution Animals Humans Circadian rhythm rhythms Photolyase 030304 developmental biology Evolutionary Biology lcsh:R DNA photolyase gene-expression Cryptochromes HEK293 Cells repair Luminescent Measurements NIH 3T3 Cells lcsh:Q Gene Function Physiological Processes Chronobiology 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE, 6(8) PLoS ONE, Vol 6, Iss 8, p e23447 (2011) PLoS One (print), 6(8). Public Library of Science PLoS ONE 6 (2011) 8 PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0023447 |
| Popis: | Despite the sequence and structural conservation between cryptochromes and photolyases, members of the cryptochrome/photolyase (flavo) protein family, their functions are divergent. Whereas photolyases are DNA repair enzymes that use visible light to lesion-specifically remove UV-induced DNA damage, cryptochromes act as photoreceptors and circadian clock proteins. To address the functional diversity of cryptochromes and photolyases, we investigated the effect of ectopically expressed Arabidopsis thaliana (6-4) PP photolyase and Potorous tridactylus CPD-photolyase (close and distant relatives of mammalian cryptochromes, respectively), on the performance of the mammalian cryptochromes in the mammalian circadian clock. Using photolyase transgenic mice, we show that Potorous CPD-photolyase affects the clock by shortening the period of behavioral rhythms. Furthermore, constitutively expressed CPD-photolyase is shown to reduce the amplitude of circadian oscillations in cultured cells and to inhibit CLOCK/BMAL1 driven transcription by interacting with CLOCK. Importantly, we show that Potorous CPD-photolyase can restore the molecular oscillator in the liver of (clock-deficient) Cry1/Cry2 double knockout mice. These data demonstrate that a photolyase can act as a true cryptochrome. These findings shed new light on the importance of the core structure of mammalian cryptochromes in relation to its function in the circadian clock and contribute to our further understanding of the evolution of the cryptochrome/photolyase protein family. |
| Databáze: | OpenAIRE |
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