Cell-cycle regulated transcription associates with DNA replication timing in yeast and human.

Cell-cycle regulated transcription associates with DNA replication timing in yeast and human.
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DOI:
10.1186/gb-2013-14-10-r111
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发表时间:
2013
期刊:
影响因子:
12.3
通讯作者:
Fraser HB
Fraser HB
中科院分区:
生物学1区
文献类型:
--
作者:
Fraser HB

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真核 DNA 复制遵循特定的时间程序,某些基因组区域始终比其他区域更早复制,但决定该程序的因素很大程度上未知。迄今为止,在所有研究的植物和动物物种中,已观察到高度转录的区域在早期 S 期复制,但这种关系被认为在芽殖酵母和裂殖酵母中都不存在。对于任何物种,细胞周期调节的转录和复制时间之间没有关联的报道。在这里,我展示了在出芽酵母、裂殖酵母和人类中,S 期转录程度最高的基因复制较早,而那些在 S 期抑制的基因复制较晚。其他细胞周期阶段的转录要么与复制时间呈现相反的相关性,要么没有关系。这种关系在复制的晚激发起点附近最强,这与之前提出的模型(复制时间可能影响转录)不一致,而是表明了一种潜在机制,涉及在 S 期招募限制性复制起始因子。这些结果表明,S 期转录可能是真核生物 DNA 复制时间的重要决定因素,这可以解释转录和复制时间之间既定的关联。
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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