Circadian oscillation of nucleotide excision repair in mammalian brain

被引:158
作者
Kang, Tae-Hong [1 ]
Reardon, Joyce T. [1 ]
Kemp, Michael [1 ]
Sancar, Aziz [1 ]
机构
[1] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
cancer treatment; chronotherapy; circadian clock; xeroderma pigmentosum A; DNA-DAMAGE; MECHANISMS; RHYTHMS; CLOCK;
D O I
10.1073/pnas.0812638106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2864 / 2867
页数:4
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