Quantitative, genome-wide analysis of eukaryotic replication initiation and termination.

Quantitative, genome-wide analysis of eukaryotic replication initiation and termination.
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DOI:
10.1016/j.molcel.2013.03.004
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发表时间:
2013-04-11
期刊:
影响因子:
16
通讯作者:
Whitehouse, Iestyn
Whitehouse, Iestyn
中科院分区:
生物学1区
文献类型:
--
作者:
McGuffee, Sean R.;Smith, Duncan J.;Whitehouse, Iestyn

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DNA复制的许多基本方面,如DNA合成起始和终止的确切位置,使用起始点的频率以及转录如何影响分叉进程,都知之甚少。通过冈崎片段的深度测序,我们全面记录了整个S。酿酒酵母基因组;这允许系统分析起始、起源效率、叉进展和终止。我们发现,前导链起始优先发生在复制起点的无核小体区域内。使用一种菌株,其中晚期起源可以诱导火灾早期,我们表明,复制终止是一个很大程度上被动的现象,不依赖于顺式作用序列或复制叉暂停。复制模式主要是由动力学的起源射击,使我们能够重建全染色体的时间配置文件从异步文化。
Many fundamental aspects of DNA replication, such as the exact locations where DNA synthesis is initiated and terminated, how frequently origins are used, and how fork progression is influenced by transcription, are poorly understood. Via the deep-sequencing of Okazaki fragments, we comprehensively document replication fork directionality throughout the S. cerevisiae genome; this permits the systematic analysis of initiation, origin efficiency, fork progression and termination. We show that leading-strand initiation preferentially occurs within a nucleosome-free region at replication origins. Using a strain in which late origins can be induced to fire early, we show that replication termination is a largely passive phenomenon that does not rely on cis-acting sequences or replication fork pausing. The replication profile is predominantly determined by the kinetics of origin firing, allowing us to reconstruct chromosome-wide timing profiles from an asynchronous culture.
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