Control of skin cancer by the circadian rhythm
- Departments of aBiochemistry and Biophysics,
- cPathology and Laboratory Medicine,
- bLineberger Comprehensive Cancer Center, and
- dCenter for Environmental Health and Susceptibility, University of North Carolina School of Medicine, Chapel Hill, NC 27599; and
- eCell Signaling and Cancer Group, Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695
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Contributed by Aziz Sancar, September 16, 2011 (sent for review August 24, 2011)

Abstract
Skin cancer is the most common form of cancer in the United States. The main cause of this cancer is DNA damage induced by the UV component of sunlight. In humans and mice, UV damage is removed by the nucleotide excision repair system. Here, we report that a rate-limiting subunit of excision repair, the xeroderma pigmentosum group A (XPA) protein, and the excision repair rate exhibit daily rhythmicity in mouse skin, with a minimum in the morning and a maximum in the afternoon/evening. In parallel with the rhythmicity of repair rate, we find that mice exposed to UV radiation (UVR) at 4:00 AM display a decreased latency and about a fivefold increased multiplicity of skin cancer (invasive squamous cell carcinoma) than mice exposed to UVR at 4:00 PM. We conclude that time of day of exposure to UVR is a contributing factor to its carcinogenicity in mice, and possibly in humans.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: aziz_sancar{at}med.unc.edu.
Author contributions: S.G. and A.S. designed research; S.G. performed research; S.G. and C.P.S. contributed new reagents/analytic tools; S.G., C.P.S., W.K.K., R.C.S., and A.S. analyzed data; and S.G., C.P.S., W.K.K., R.C.S., and A.S. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1115249108/-/DCSupplemental.
Freely available online through the PNAS open access option.
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