Laboratory of Virology, Wageningen University, Wageningen, the Netherlands.
J Biol Rhythms. 2012 Feb;27(1):3-11. doi: 10.1177/0748730411429665.
Cryptochromes and photolyases belong to the same family of flavoproteins but, despite being structurally conserved, display distinct functions. Photolyases use visible light to repair ultraviolet-induced DNA damage. Cryptochromes, however, function as blue-light receptors, circadian photoreceptors, or repressors of the CLOCK/BMAL1 heterodimer, the transcription activator controlling the molecular circadian clock. Here, we present evidence that the functional divergence between cryptochromes and photolyases is not so univocal. Chrysodeixis chalcites nucleopolyhedrovirus possesses 2 photolyase-like genes: phr1 and phr2. We show that PHR1 and PHR2 are able to bind the CLOCK protein. Only for PHR2, however, the physical interaction with CLOCK represses CLOCK/BMAL1-driven transcription. This result shows that binding of photolyase per se is not sufficient to inhibit the CLOCK/BMAL1 heterodimer. PHR2, furthermore, affects the oscillation of immortalized mouse embryonic fibroblasts, suggesting that PHR2 can regulate the molecular circadian clock. These findings are relevant for further understanding the evolution of cryptochromes and photolyases as well as behavioral changes induced in insects by baculoviruses.
隐花色素和光解酶属于黄素蛋白家族，但尽管结构保守，却具有不同的功能。光解酶利用可见光修复紫外线诱导的 DNA 损伤。然而，隐花色素作为蓝光受体、生物钟光感受器或 CLOCK/BMAL1 异二聚体的抑制剂发挥作用，CLOCK/BMAL1 异二聚体是控制分子生物钟的转录激活剂。在这里，我们提供的证据表明，隐花色素和光解酶之间的功能分歧并非如此单一。Chrysodeixis chalcites 核型多角体病毒拥有 2 个光解酶样基因：phr1 和 phr2。我们表明 PHR1 和 PHR2 能够结合 CLOCK 蛋白。然而，只有 PHR2 与 CLOCK 的物理相互作用才能抑制 CLOCK/BMAL1 驱动的转录。这一结果表明，光解酶的结合本身不足以抑制 CLOCK/BMAL1 异二聚体。此外，PHR2 还影响永生的小鼠胚胎成纤维细胞的振荡，表明 PHR2 可以调节分子生物钟。这些发现对于进一步了解隐花色素和光解酶的进化以及杆状病毒诱导昆虫行为变化具有重要意义。
