Brunner Michael, Schafmeier Tobias
Biochemie-Zentrum der Universität Heidelberg, 69120 Heidelberg, Germany.
Genes Dev. 2006 May 1;20(9):1061-74. doi: 10.1101/gad.1410406.
Circadian clocks are self-sustained oscillators modulating rhythmic transcription of large numbers of genes. Clock-controlled gene expression manifests in circadian rhythmicity of many physiological and behavioral functions. In eukaryotes, expression of core clock components is organized in a network of interconnected positive and negative feedback loops. This network is thought to constitute the pacemaker that generates circadian rhythmicity. The network of interconnected loops is embedded in a supra-net via a large number of interacting factors that affect expression and function of core clock components on transcriptional and post-transcriptional levels. In particular, phosphorylation and dephosphorylation of clock components are critical processes ensuring robust self-sustained circadian rhythmicity and entrainment of clocks to external cues. In cyanobacteria, three clock proteins have the capacity to generate a self-sustained circadian rhythm of autophosphorylation and dephosphorylation independent of transcription and translation. This phosphorylation rhythm regulates the function of these clock components, which then facilitate rhythmic gene transcription, including negative feedback on their own genes. In this article, we briefly present the mechanism of clock function in cyanobacteria. We then discuss in detail the contribution of transcriptional feedback and protein phosphorylation to various functional aspects of the circadian clock of Neurospora crassa.
昼夜节律钟是自我维持的振荡器，可调节大量基因的节律性转录。生物钟控制的基因表达表现为许多生理和行为功能的昼夜节律性。在真核生物中，核心生物钟组件的表达由相互连接的正反馈和负反馈环网络组成。该网络被认为构成了产生昼夜节律性的起搏器。相互连接的环网络通过大量相互作用的因子嵌入到一个超网络中，这些因子在转录和转录后水平上影响核心生物钟组件的表达和功能。特别是，生物钟组件的磷酸化和去磷酸化是确保强大的自我维持昼夜节律性以及使生物钟与外部线索同步的关键过程。在蓝细菌中，三种生物钟蛋白能够产生独立于转录和翻译的自我维持的自磷酸化和去磷酸化昼夜节律。这种磷酸化节律调节这些生物钟组件的功能，进而促进节律性基因转录，包括对其自身基因的负反馈。在本文中，我们简要介绍了蓝细菌中生物钟功能的机制。然后，我们详细讨论了转录反馈和蛋白质磷酸化对粗糙脉孢菌昼夜节律钟各个功能方面的贡献。
