Phase resetting of the mammalian circadian clock by DNA damage
العنوان: | Phase resetting of the mammalian circadian clock by DNA damage |
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المؤلفون: | Roelof A. Hut, Eugin Destici, Malgorzata Oklejewicz, Roel C. Janssens, Gijsbertus T. J. van der Horst, Filippo Tamanini |
المساهمون: | Hut lab, Molecular Genetics |
المصدر: | Current Biology, 18(4), 286-291. CELL PRESS Current Biology, 18(4), 286-291. Cell Press |
بيانات النشر: | Cell Press, 2008. |
سنة النشر: | 2008 |
مصطلحات موضوعية: | Male, DNA damage, PROTEINS, Period (gene), Circadian clock, Gene Expression, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Biology, General Biochemistry, Genetics and Molecular Biology, Cell Line, Mice, SDG 3 - Good Health and Well-being, Biological Clocks, KINASE ATM, Ultraviolet light, Animals, Circadian rhythm, ATAXIA-TELANGIECTASIA, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Suprachiasmatic nucleus, Tumor Suppressor Proteins, COMPONENTS, DNA, SUPRACHIASMATIC NUCLEUS, EVOLUTION, Circadian Rhythm, Rats, Cell biology, TUMOR SUPPRESSION, DNA-Binding Proteins, Mice, Inbred C57BL, CLOCK, BIOLOGICAL CLOCK, Biochemistry, Gamma Rays, CELLS, RESPONSE CURVES, General Agricultural and Biological Sciences, DNA Damage, Signal Transduction |
الوصف: | SummaryTo anticipate the momentum of the day, most organisms have developed an internal clock that drives circadian rhythms in metabolism, physiology, and behavior [1]. Recent studies indicate that cell-cycle progression and DNA-damage-response pathways are under circadian control [2–4]. Because circadian output processes can feed back into the clock, we investigated whether DNA damage affects the mammalian circadian clock. By using Rat-1 fibroblasts expressing an mPer2 promoter-driven luciferase reporter, we show that ionizing radiation exclusively phase advances circadian rhythms in a dose- and time-dependent manner. Notably, this in vitro finding translates to the living animal, because ionizing radiation also phase advanced behavioral rhythms in mice. The underlying mechanism involves ATM-mediated damage signaling as radiation-induced phase shifting was suppressed in fibroblasts from cancer-predisposed ataxia telangiectasia and Nijmegen breakage syndrome patients. Ionizing radiation-induced phase shifting depends on neither upregulation or downregulation of clock gene expression nor on de novo protein synthesis and, thus, differs mechanistically from dexamethasone- and forskolin-provoked clock resetting [5]. Interestingly, ultraviolet light and tert-butyl hydroperoxide also elicited a phase-advancing effect. Taken together, our data provide evidence that the mammalian circadian clock, like that of the lower eukaryote Neurospora [6], responds to DNA damage and suggest that clock resetting is a universal property of DNA damage. |
وصف الملف: | application/pdf |
تدمد: | 1879-0445 0960-9822 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea88fc95123dd1210271471b77512008 https://pure.eur.nl/en/publications/29d44e7c-7525-4246-b488-c05aa4c26367 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....ea88fc95123dd1210271471b77512008 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 18790445 09609822 |
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