The role of mammalian circadian proteins in normal physiology and genotoxic stress responses

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. (c) 2007, Elsevier Inc.