Cryptochrome, Circadian Cycle, Cell Cycle Checkpoints, and Cancer Public Deposited

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  • March 20, 2019
Creator
  • Gauger, Michele Ann
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
Abstract
  • The mammalian circadian clock is a global regulatory system that controls many aspects of physiology, including behavior, metabolism, cell cycle progression, and overall fitness. CRYPTOCHROMES (CRYs) are core elements of the mammalian circadian clock, and loss of CRY expression leads to arrythmicity. Although much work has been done analyzing the mammalian clock, the molecular mechanisms underlying the clock and resulting from its disruption are still largely unknown. There is growing evidence that circadian rhythm disruption in both humans and rodents leads to predisposition to cancer and poor prognosis; however, it has not been determined if cancer predisposition is a hallmark of all types of clock disruption. Here I present evidence that arrhythmic Cry1-/-Cry2-/- mice possess an intact DNA damage checkpoint and repair system and are not predisposed to ionizing radiation-induced cancers relative to wild-type mice. In addition, experiments were conducted to determine the direct effect, if any, that CRY1 exerts on CLOCK-BMAL1 heterodimer DNA-binding. I find that CRY1 neither inhibits nor modifies the DNA binding of a heterodimer consisting of BMAL1 and a 342-amino acid fragment of CLOCK (CLOCK342) in vitro. However, this does not rule out the possibility that CRY1 could have an effect on a heterodimer of BMAL1 and full-length CLOCK in vitro.
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  • Sancar, Aziz
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