Whitmore D, Cermakian N, Crosio C, Foulkes N S, Pando M P, Travnickova Z, Sassone-Corsi P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, CU de Strasbourg, Illkirch, France.
Biol Chem. 2000 Sep-Oct;381(9-10):793-800. doi: 10.1515/BC.2000.102.
The vertebrate circadian clock was thought to be highly localized to specific anatomical structures: the mammalian suprachiasmatic nucleus (SCN), and the retina and pineal gland in lower vertebrates. However, recent findings in the zebrafish, rat and in cultured cells have suggested that the vertebrate circadian timing system may in fact be highly distributed, with most if not all cells containing a clock. Our understanding of the clock mechanism has progressed extensively through the use of mutant screening and forward genetic approaches. The first vertebrate clock gene was identified only a few years ago in the mouse by such an approach. More recently, using a syntenic comparative genetic approach, the molecular basis of the the tau mutation in the hamster was determined. The tau gene in the hamster appears to encode casein kinase 1 epsilon, a protein previously shown to be important for PER protein turnover in the Drosophila circadian system. A number of additional clock genes have now been described. These proteins appear to play central roles in the transcription-translation negative feedback loop responsible for clock function. Post-translational modification, protein dimerization and nuclear transport all appear to be essential features of how clocks are thought to tick.
哺乳动物的视交叉上核（SCN），以及低等脊椎动物的视网膜和松果体。然而，最近在斑马鱼、大鼠以及培养细胞中的研究结果表明，脊椎动物的昼夜节律计时系统实际上可能高度分散，大多数甚至所有细胞都含有生物钟。通过使用突变筛选和正向遗传学方法，我们对生物钟机制的理解有了很大进展。仅仅在几年前，通过这种方法在小鼠中鉴定出了第一个脊椎动物生物钟基因。最近，利用同线比较遗传学方法，确定了仓鼠tau突变的分子基础。仓鼠中的tau基因似乎编码酪蛋白激酶1ε，该蛋白先前已被证明在果蝇昼夜节律系统中对PER蛋白周转很重要。现在已经描述了许多其他生物钟基因。这些蛋白质似乎在负责生物钟功能的转录-翻译负反馈环中发挥核心作用。翻译后修饰、蛋白质二聚化和核转运似乎都是生物钟运行机制的基本特征。
