Mechanisms regulating S phase progression in mammalian cells

Mechanisms regulating S phase progression in mammalian cells
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DOI:
10.2741/3523
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发表时间:
2009-01-01
影响因子:
3.1
通讯作者:
Jackson, Dean A.
Jackson, Dean A.
中科院分区:
生物学4区
文献类型:
--
作者:
Maya-Mendoza, Apolinar;Tang, Chi W.;Jackson, Dean A.

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细胞增殖需要将相同的遗传物质传递给在有丝分裂过程中形成的子细胞。遗传拷贝是在前一个间期产生的,此时母细胞的DNA只复制一次。虽然生物学中很少有过程受到这种精确度的调节,但其根本重要性不可低估,因为缺陷可能会损害遗传完整性并最终导致癌症。人类基因组在二倍体细胞中的复制发生在细胞周期的S期。在这近似10小时的时间内,约10%的复制单位(复制子)在任何时候都是活跃的,即使所有潜在的起始位点(起点)都在S期开始之前建立。至关重要的是,调节起源选择和确定结构化复制程序的机制仍有待确定。我们回顾了最近的进展,了解S期的结构和调节,并开发了一个模型,我们认为最好的描述了S期程序在人类细胞。
Cell proliferation demands that identical genetic material is passed to daughter cells that form during mitosis. Genetic copies are produced during the preceding interphase, when DNA of the mother cell is copied exactly once. While few processes in biology are regulated with this precision, the fundamental importance cannot be understated as defects might compromise genetic integrity and ultimately lead to cancer. Replication of the human genome in diploid cells occurs during S phase of the cell cycle. Throughout this similar to 10h period, about 10% of replication units - replicons - are active at any time, even though all potential initiation sites - origins - are established before the onset of S phase. Crucially, the mechanisms that regulate origin selection and define a structured replication programme remain to be defined. We review recent progress in understanding the structure and regulation of S phase and develop a model that we believe best describes the S phase programme in human cells.