细胞周期调控的转录与酵母和人的DNA复制时序相关
Cell-cycle regulated transcription associates with DNA replication timing in yeast and human
摘要：
真核DNA复制遵循特定的时间程序，一些基因组区域始终比其他区域更早复制，但决定这一程序的因素在很大程度上是未知的。在迄今为止研究的所有植物和动物物种中，都观察到高度转录的区域在早期S期复制，但这种关系被认为是芽殖酵母和裂殖酵母都不存在的。目前尚无任何物种的细胞周期调节转录与复制时机之间存在关联的报道。在这里，我表明，在芽殖酵母，裂殖酵母，和人类，在S期复制早期最高度转录的基因，而那些在S期抑制复制后期。在其他细胞周期阶段的转录显示与复制时间相反的相关性，或没有关系。这种关系在晚发复制起点附近是最强的，这与先前提出的模型不一致-复制时间可能会影响转录-而是表明了一种潜在的机制，涉及在S期招募限制性复制起始因子。这些结果表明，S期转录可能是一个重要的决定因素的DNA复制时间在真核生物，这可能解释了转录和复制时间之间的良好建立的关联。
英文摘要：
Eukaryotic DNA replication follows a specific temporal program, with some genomic regions consistently replicating earlier than others, yet what determines this program is largely unknown. Highly transcribed regions have been observed to replicate in early S-phase in all plant and animal species studied to date, but this relationship is thought to be absent from both budding yeast and fission yeast. No association between cell-cycle regulated transcription and replication timing has been reported for any species. Here I show that in budding yeast, fission yeast, and human, the genes most highly transcribed during S-phase replicate early, whereas those repressed in S-phase replicate late. Transcription during other cell-cycle phases shows either the opposite correlation with replication timing, or no relation. The relationship is strongest near late-firing origins of replication, which is not consistent with a previously proposed model -- that replication timing may affect transcription -- and instead suggests a potential mechanism involving the recruitment of limiting replication initiation factors during S-phase. These results suggest that S-phase transcription may be an important determinant of DNA replication timing across eukaryotes, which may explain the well-established association between transcription and replication timing.
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