Deregulation of the circadian clock constitutes a significant factor in tumorigenesis: a clockwork cancer. Part I: clocks and clocking machinery

生物钟紊乱是肿瘤发生的重要因素:一种“时钟型癌症”。第一部分:生物钟及其调控机制

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Abstract

Many physiological processes occur in a rhythmic fashion, consistent with a 24-h cycle. The central timing of the day/night rhythm is set by a master clock, located in the suprachiasmatic nucleus (a tiny region in the hypothalamus), but peripheral clocks exist in different tissues, adjustable by cues other than light (temperature, food, hormone stimulation, etc.), functioning autonomously to the master clock. Presence of unrepaired DNA damage may adjust the circadian clock so that the phase in which checking for damage and DNA repair normally occurs is advanced or extended. The expression of many of the genes coding for proteins functioning in DNA damage-associated response pathways and DNA repair is directly or indirectly regulated by the core clock proteins. Setting up the normal rhythm of the circadian cycle also involves oscillating changes in the chromatin structure, allowing differential activation of various chromatin domains within the 24-h cycle.

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