Determining the Effect of Cryptochrome Loss and Circadian Clock Disruption on Tumorigenesis in Mice
Abstract
It has recently been reported that disruption of the circadian clock leads to increased breast cancer risk in humans and to a high rate of ionizing radiation (IR)-induced tumors in mice. Cryptochrome 1 and 2 proteins are core components of the mammalian circadian clock and mice mutated in both genes are arrhythmic. We tested Cry1-/-Cry2-/- mice and fibroblasts derived from these mice for radiation induced cancer and killing, and DNA damage checkpoint and killing, respectively. We find that the arrhythmic mice and fibroblasts are indistinguishable from wild-type controls with respect to their radiation-induced morbidity and mortality. We also find that upregulation of the cell cycle kinase Weel in the absence of Cryptochromes does not affect the DNA damage checkpoint and that c-Myc regulation is normal in the absence of Cryptochromes. Our data suggest that the disruption of the circadian clock per se does not predispose mice to cancer. It appears that the core clock proteins may participate in DNA damage checkpoints in manners unique to each core clock protein and as a consequence circadian disruption may or may not predispose mice to cancer depending on the specific mechanism of disruption.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA435115
Entities
People
- Michele A. Gauger
Organizations
- University of North Carolina at Chapel Hill