Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260, USA.
FEBS Lett. 2010 Jun 18;584(12):2618-25. doi: 10.1016/j.febslet.2010.03.017. Epub 2010 Mar 15.
Mammalian cells possess a cell-autonomous molecular clock which controls the timing of many biochemical reactions and hence the cellular response to environmental stimuli including genotoxic stress. The clock consists of an autoregulatory transcription-translation feedback loop made up of four genes/proteins, BMal1, Clock, Cryptochrome, and Period. The circadian clock has an intrinsic period of about 24 h, and it dictates the rates of many biochemical reactions as a function of the time of the day. Recently, it has become apparent that the circadian clock plays an important role in determining the strengths of cellular responses to DNA damage including repair, checkpoints, and apoptosis. These new insights are expected to guide development of novel mechanism-based chemotherapeutic regimens.
哺乳动物细胞拥有自主分子钟，它控制着许多生化反应的时间，从而控制细胞对环境刺激（包括遗传毒性应激）的反应。该时钟由一个由四个基因/蛋白（BMal1、Clock、Cryptochrome 和 Period）组成的自动调节转录-翻译反馈环构成。昼夜节律钟的固有周期约为 24 小时，它根据一天中的时间来决定许多生化反应的速度。最近，昼夜节律钟在决定细胞对 DNA 损伤（包括修复、检查点和细胞凋亡）的反应强度方面起着重要作用，这一点已变得显而易见。这些新的见解有望指导基于新机制的化疗方案的开发。
