Dunlap J C, Feldman J F
Department of Biology, University of California, Santa Cruz 95064.
Proc Natl Acad Sci U S A. 1988 Feb;85(4):1096-100. doi: 10.1073/pnas.85.4.1096.
Inhibitors of protein synthesis reset the biological clocks of many organisms. This has been interpreted to mean either that the synthesis per se of proteins is a step in the oscillatory feedback loop or merely that certain unstable protein(s) are required at certain times of the cycle to complete the feedback loop. We report here that Neurospora strains bearing the clock mutation frq-7 are relatively insensitive to the resetting action of the protein-synthesis-inhibitor cycloheximide. Protein synthesis itself in this mutant is inhibited by the drug to the same extent as in wild type. Since the clock of frq-7 continues to run relatively unimpeded even in the virtual absence of protein synthesis, it is unlikely that synthesis per se can be a part of the feedback cycle. Rather, we suggest that for normal operation of the Neurospora clock, certain protein(s) with a high turnover rate are required daily and, thus, must be resynthesized each day (at least) during discrete times in the cycle. The frq-7 mutation simultaneously alters several distinct clock characteristics--period length, temperature compensation, and resetting by cycloheximide. A model is presented to unify these observations.
蛋白质合成抑制剂可重置许多生物体的生物钟。这被解释为要么蛋白质的合成本身是振荡反馈回路中的一个步骤，要么仅仅意味着在周期的特定时间需要某些不稳定的蛋白质来完成反馈回路。我们在此报告，携带生物钟突变frq - 7的粗糙脉孢菌菌株对蛋白质合成抑制剂环己酰亚胺的重置作用相对不敏感。该药物对这种突变体中蛋白质合成本身的抑制程度与对野生型的抑制程度相同。由于即使在几乎没有蛋白质合成的情况下，frq - 7的生物钟仍能相对不受阻碍地运行，所以合成本身不太可能是反馈循环的一部分。相反，我们认为，对于粗糙脉孢菌生物钟的正常运行，每天都需要某些周转率高的蛋白质，因此，每天（至少）必须在周期中的特定时间重新合成这些蛋白质。frq - 7突变同时改变了几个不同的生物钟特征——周期长度、温度补偿以及环己酰亚胺的重置作用。本文提出了一个模型来统一这些观察结果。
