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Contributed by Aziz Sancar, December 11, 2008 (sent for review December 3, 2008)
Abstract
The circadian clock regulates the daily rhythms in the physiology and behavior of many organisms, including mice and humans. These cyclical changes at molecular and macroscopic levels affect the organism's response to environmental stimuli such as light and food intake and the toxicity and efficacy of chemo- and radiotherapeutic agents. In this work, we investigated the circadian behavior of the nucleotide excision repair capacity in the mouse cerebrum to gain some insight into the optimal circadian time for favorable therapeutic response with minimal side effects in cancer treatment with chemotherapeutic drugs that produce bulky adducts in DNA. We find that nucleotide excision repair activity in the mouse cortex is highest in the afternoon/evening hours and is at its lowest in the night/early morning hours. The circadian oscillation of the repair capacity is caused at least in part by the circadian oscillation of the xeroderma pigmentosum A DNA damage recognition protein.
Footnotes
- 1To whom correspondence should be addressed. E-mail: aziz_sancar{at}med.unc.edu
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Author contributions: T.-H.K. and A.S. designed research; T.-H.K., J.T.R., and M.K. performed research; T.-H.K., J.T.R., and M.K. contributed new reagents/analytic tools; T.-H.K., J.T.R., M.K., and A.S. analyzed data; and T.-H.K., J.T.R., M.K., and A.S. wrote the paper.
The authors declare no conflict of interest.
Freely available online through the PNAS open access option.
- © 2009 by The National Academy of Sciences of the USA
Circadian oscillation of nucleotide excision repair in mammalian brain
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