Kondratov Roman V, Gorbacheva Victoria Y, Antoch Marina P
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Curr Top Dev Biol. 2007;78:173-216. doi: 10.1016/S0070-2153(06)78005-X.
The last two decades have significantly advanced our understanding of the organization of the circadian system at all levels of regulation-molecular, cellular, tissue, and systemic. It has been recognized that the circadian system represents a complex temporal regulatory network, which plays an important role in synchronizing various biological processes within an organism and coordinating them with the environment. It is believed that deregulation of this synchronization may result in the development of various pathologies. However, recent studies using various circadian mutant mouse models have demonstrated that at least some of the components of the molecular oscillator are actively involved in physiological processes not directly related to their role in the circadian clock. The growing amount of evidence suggests that, in addition to their circadian function, circadian proteins are important in maintaining tissue homeostasis under normal and stress conditions. In this chapter, we will summarize recent data about the regulation of the mammalian molecular circadian oscillator and will focus on a new role of the circadian system and individual circadian proteins in the organism's physiology and response to genotoxic stress in connection with diseases treatment and prevention.
在过去二十年里，我们对昼夜节律系统在分子、细胞、组织和系统等各个调控层面的组织架构有了显著深入的了解。人们已经认识到，昼夜节律系统是一个复杂的时间调控网络，在使生物体内各种生物过程同步并与环境协调方面发挥着重要作用。据信，这种同步失调可能导致各种疾病的发生。然而，最近使用各种昼夜节律突变小鼠模型进行的研究表明，分子振荡器的至少一些组件积极参与了与其在生物钟中的作用没有直接关系的生理过程。越来越多的证据表明，除了其昼夜节律功能外，昼夜节律蛋白在正常和应激条件下维持组织稳态方面也很重要。在本章中，我们将总结有关哺乳动物分子昼夜节律振荡器调控的最新数据，并将重点关注昼夜节律系统和单个昼夜节律蛋白在生物体生理以及与疾病治疗和预防相关的基因毒性应激反应中的新作用。
