Determining the Effect of Cryptochrome Loss and Circadian Clock Disruption on Tumorigenesis in Mice

摘要

Circadian clock disruption may be correlated to increased risk of breast cancer in humans and has been linked to tumor progression and development in mice. We have previously reported that circadian clock disruption by loss of Cryptochrome expression does not cause DNA damage checkpoint or repair defects in mammalian fibroblasts, nor does it cause an increase in tumor predisposition or sensitivity to ionizing radiation in mice. Also of interest is the effect of Cryptochrome loss on gene expression; specifically, we are interested in the role CRYPTOCHROME protein plays in inhibition of circadian gene expression. We find that CRY does not affect the DNA binding of the circadian transcriptional activator CLOCK342-BMAL1, consisting of a 342-amino acid fragment of mammalian CLOCK and full-length BMAL1. In addition, preliminary results indicate that CRY does not affect the DNA binding of CLOCK-BMAL1, consisting of full-length mammalian CLOCK and BMAL1 proteins; however, these results are not yet entirely conclusive and will be investigated further in the future.