Faculty of Life Sciences, University of Manchester, MIB, 131 Princess Street, Manchester, M1 7DN, UK.
Chromosome Res. 2010 Jan;18(1):163-78. doi: 10.1007/s10577-010-9114-2.
The control of DNA replication is of fundamental importance as cell proliferation demands that identical copies of the genetic material are passed to the two daughter cells that form during mitosis. These genetic copies are generated in the preceding S phase, where the entire DNA complement of the mother cell must be copied exactly once. As part of this process, it is known that different regions of mammalian genomes are replicated at specific times of a temporally defined replication programme. The key feature of this programme is that active genes in euchromatin are replicated before inactive ones in heterochromatin. This separation of S phase into periods where different classes of chromatin are duplicated is important in maintaining changes in gene expression that define individual cell types. Recent attempts to understand the structure of the S-phase timing programme have focused on the use of genome-wide strategies that inevitably use DNA isolated from large cell populations for analysis. However, this approach provides a composite view of events that occur within a population without knowledge of the cell-to-cell variability across the population. In this review, we attempt to combine information generated using genome-wide and single cell strategies in order to develop a coherent molecular understanding of S-phase progression. During this integration, we have explored how available information can be introduced into a modelling environment that best describes S-phase progression in mammalian cells.
DNA 复制的控制至关重要，因为细胞增殖要求遗传物质的相同副本传递给有丝分裂过程中形成的两个子细胞。这些遗传副本是在前一个 S 期生成的，在此期间，母细胞的整个 DNA 必须完全复制一次。作为这个过程的一部分，已知哺乳动物基因组的不同区域在时间定义的复制程序的特定时间被复制。该程序的关键特征是常染色质中的活性基因在异染色质中的非活性基因之前复制。将 S 期分为不同类别的染色质复制的时期，对于维持定义单个细胞类型的基因表达变化很重要。最近，人们试图了解 S 期定时程序的结构，重点是使用全基因组策略，这些策略不可避免地使用从大细胞群中分离的 DNA 进行分析。然而，这种方法提供了在没有了解整个群体中细胞间变异性的情况下发生事件的综合视图。在这篇综述中，我们试图结合使用全基因组和单细胞策略生成的信息，以发展对 S 期进展的连贯分子理解。在这个整合过程中，我们探索了如何将可用信息引入到最能描述哺乳动物细胞 S 期进展的建模环境中。
