Signal transduction mechanisms of cryptochrome Public Deposited

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  • March 21, 2019
  • Partch, Carrie L.
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
  • Photolyase and cryptochrome flavoproteins help living organisms manage the deleterious and beneficial effects of sunlight. Photolyase maintains genome integrity by reversing UV-induced DNA damage with near-UV/blue-light, and cryptochromes act as bluelight photosensory receptors to regulate growth in plants and entrainment of circadian rhythms in both plants and animals. Although photolyase and cryptochrome are highly structurally homologous and the photocycle of photolyase is known in great detail, we do not currently understand how cryptochromes signal in response to light. It is hypothesized that cryptochrome, like photolyase, employs light-driven electron transfer to initiate signaling, although the photocycle and other downstream signaling events remain to be described in detail. The studies described here were designed to take advantage of differences and similarities in the known functions of photolyases and cryptochromes in order to characterize the signaling mechanisms of cryptochromes. An examination of the structural and biochemical properties of plant and animal cryptochromes demonstrates that although they evolved independently from functionally distinct photolyase progenitors, they possess several unexpected similarities, demonstrating convergence in the evolution of cryptochromes. The implications of these results for the cryptochrome photocycle are discussed. Metazoan cryptochromes additionally have a critical, light-independent function in the molecular clock that engenders circadian rhythms. Other studies have shown that iv cryptochromes act as transcriptional repressors in the major transcription/translation feedback loop of the clock. I studied the interaction of mammalian cryptochromes with protein phosphatase 5 (PP5) and show that inhibition of PP5 by cryptochrome modulates the activity of the major clock kinase, casein kinase I epsilon. PP5 is required for proper cycling of the clock; therefore, these data provide the first demonstration of the role of a phosphatase in the mammalian circadian clock. Furthermore, they suggest that cryptochromes regulate the molecular clock by both transcriptional and posttranslational mechanisms.
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  • Sancar, Aziz
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  • University of North Carolina at Chapel Hill
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