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Abstract

Many aspects of physiology are regulated in a temporal manner by an internal clock that anticipates the time of day and directs physiological processes accordingly (1). In mammals, cellular processes such as cholesterol and heme biosynthesis, temperature and hormonal rhythms, and the sleep wake cycle are all “timed” by the circadian clock to occur at appropriate time periods in the absence of environmental cues (2). Remarkably, in mammals these processes are controlled by a small nucleus in the hypothalamus, the suprachiasmatic nucleus (SCN), which harbors the “master” oscillator, or core clock. This master oscillator, in turn, synchronizes peripheral clocks that regulate physiology in a tissue- and time-dependent manner. This timekeeping mechanism is composed of three essential elements: (i) a light input pathway that allows for resetting with a changing environment, (i) a core oscillator that keeps track of time, and (iii) the output of the clock that dictates circadian controlled physiology (Figure 1). The past thirty years of study has elucidated many components of the core circadian oscillator, including a basic model for clock mechanism in flies and mammals (3). In fact, the first clues to mammalian circadian mechanism began with “P” in PAS and the study of the fruit fly.

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Hogenesch, J.B., Kay, S.A. (2003). PAS Proteins in the Mammalian Circadian Clock. In: Crews, S.T. (eds) PAS Proteins: Regulators and Sensors of Development and Physiology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0515-0_10

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