DNA replication origins, ORC/DNA interaction, and assembly of pre-replication complex in eukaryotes.
DNA replication origins, ORC/DNA interaction, and assembly of pre-replication complex in eukaryotes.
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DOI：
10.1093/abbs/gmq048
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发表时间：
2010-07
影响因子：
3.7
通讯作者：
J. Sun;D. Kong
中科院分区：
文献类型：
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作者：
J. Sun;D. Kong
真核细胞的染色体DNA复制是高度复杂和精细调控的。由于其大的尺寸，一个典型的真核生物基因组包含数百到数万个起始位点，称为DNA复制起点，DNA合成发生在那里。多个起始位点消除了基因组大小的限制，因为只有一定数量的DNA可以在有限的时间内从一个单一的起源复制。这些多重起源的激活必须协调一致，以便染色体DNA的每个片段在每个细胞周期中精确地复制一次。尽管DNA复制是细胞生长的重要过程，其机制高度保守，但最近的研究也揭示了在起源结构、预复制复合体（pre-replication complex, pre-RC）的组装和复制起始调控方面存在显著的进化差异。在裂糖酵母的DNA复制起点中，除了必需的起点识别复合体结合位点外，还含有与Sap1蛋白结合的第二个必需元件。Sap1最近被证明是一种新的复制起始蛋白，在将起始蛋白Cdc18装载到起点并直接参与pre-RC形成中起着至关重要的作用。本文综述了酵母和后生动物中DNA复制起源的组织、pre-RC的组装以及DNA复制的启动和调控等方面的研究进展。
Chromosomal DNA replication in eukaryotic cells is highly complicated and sophisticatedly regulated. Owing to its large size, a typical eukaryotic genome contains hundreds to tens of thousands of initiation sites called DNA replication origins where DNA synthesis takes place. Multiple initiation sites remove the constraint of a genome size because only a certain amount of DNA can be replicated from a single origin in a limited time. The activation of these multiple origins must be coordinated so that each segment of chromosomal DNA is precisely duplicated only once per cell cycle. Although DNA replication is a vital process for cell growth and its mechanism is highly conserved, recent studies also reveal significant diversity in origin structure, assembly of pre-replication complex (pre-RC) and regulation of replication initiation along evolutionary lines. The DNA replication origins in the fission yeast Schizosaccharomyces pombe are found to contain a second essential element that is bound by Sap1 protein besides the essential origin recognition complex-binding site. Sap1 is recently demonstrated to be a novel replication initiation protein that plays an essential role in loading the initiation protein Cdc18 to origins and thus directly participates in pre-RC formation. In this review, we summarize the recent advance in understanding how DNA replication origins are organized, how pre-RC is assembled and how DNA replication is initiated and regulated in yeast and metazoans.