Young M W
National Science Foundation Science and Technology Center for Biological Timing, Rockefeller University, New York, New York 10021, USA.
Annu Rev Biochem. 1998;67:135-52. doi: 10.1146/annurev.biochem.67.1.135.
Molecular and genetic characterizations of circadian rhythms in Drosophila indicate that function of an intracellular pacemaker requires the activities of proteins encoded by three genes: period (per), timeless (tim), and doubletime (dbt). RNA from two of these genes, per and tim, is expressed with a circadian rhythm. Heterodimerization of PER and TIM proteins allows nuclear localization and suppression of further RNA synthesis by a PER/TIM complex. These protein interactions promote cyclical gene expression because heterodimers are observed only at high concentrations of per and tim RNA, separating intervals of RNA accumulation from times of PER/TIM complex activity. Light resets these molecular cycles by eliminating TIM. The product of dbt also regulates accumulation of per and tim RNA, and it may influence action of the PER/TIM complex. The recent discovery of PER homologues in mice and humans suggests that a related mechanism controls mammalian circadian behavioral rhythms.
果蝇昼夜节律的分子和遗传学特征表明，细胞内生物钟的功能需要三个基因所编码蛋白质的活动：周期基因（per）、无时间基因（tim）和双倍时间基因（dbt）。其中两个基因，即per和tim的RNA以昼夜节律表达。PER和TIM蛋白的异源二聚化使得PER/TIM复合物能够进行核定位并抑制进一步的RNA合成。这些蛋白质相互作用促进了周期性基因表达，因为只有在per和tim RNA浓度较高时才会观察到异源二聚体，从而将RNA积累的间隔与PER/TIM复合物活动的时间区分开来。光通过消除TIM来重置这些分子周期。dbt的产物也调节per和tim RNA的积累，并且可能影响PER/TIM复合物的作用。最近在小鼠和人类中发现了PER同源物，这表明一种相关机制控制着哺乳动物的昼夜行为节律。
