1] Center for Frontier Research, National Institute of Genetics, 1111 Yata, Mishima 411-8540, Shizuoka, Japan [2] Department of Genetics, Graduate University for Advanced Studies (SOKENDAI), 1111 Yata, Mishima 411-8540, Shizuoka, Japan [3] Japan Science and Technology Agency, CREST, 4-1-8 Honcho, Kawaguchi 332-0012, Saitama, Japan [4].
1] Center for Frontier Research, National Institute of Genetics, 1111 Yata, Mishima 411-8540, Shizuoka, Japan [2].
Nat Commun. 2014 May 8;5:3807. doi: 10.1038/ncomms4807.
Circadian rhythms of cell division have been observed in several lineages of eukaryotes, especially photosynthetic unicellular eukaryotes. However, the mechanism underlying the circadian regulation of the cell cycle and the nature of the advantage conferred remain unknown. Here, using the unicellular red alga Cyanidioschyzon merolae, we show that the G1/S regulator RBR-E2F-DP complex links the G1/S transition to circadian rhythms. Time-dependent E2F phosphorylation promotes the G1/S transition during subjective night and this phosphorylation event occurs independently of cell cycle progression, even under continuous dark or when cytosolic translation is inhibited. Constitutive expression of a phospho-mimic of E2F or depletion of RBR unlinks cell cycle progression from circadian rhythms. These transgenic lines are exposed to higher oxidative stress than the wild type. Circadian inhibition of cell cycle progression during the daytime by RBR-E2F-DP pathway likely protects cells from photosynthetic oxidative stress by temporally compartmentalizing photosynthesis and cell cycle progression.
细胞分裂的昼夜节律已在几种真核生物谱系中被观察到,特别是光合单细胞真核生物。然而,细胞周期昼夜节律调节的机制以及赋予的优势的本质仍然未知。在这里,我们使用单细胞红藻 Cyanidioschyzon merolae 表明,G1/S 调节因子 RBR-E2F-DP 复合物将 G1/S 转变与昼夜节律联系起来。依赖时间的 E2F 磷酸化促进主观夜间的 G1/S 转变,并且该磷酸化事件独立于细胞周期进程发生,即使在连续黑暗或胞质翻译被抑制时也是如此。E2F 的磷酸模拟物的组成型表达或 RBR 的耗竭使细胞周期进程与昼夜节律脱钩。这些转基因系比野生型更容易受到氧化应激的影响。RBR-E2F-DP 途径在白天抑制细胞周期进程可能通过时间上分隔光合作用和细胞周期进程来保护细胞免受光合氧化应激。