MacAlpine David M, Bell Stephen P
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Chromosome Res. 2005;13(3):309-26. doi: 10.1007/s10577-005-1508-1.
Recent advances in DNA microarray technology have enabled eukaryotic replication to be studied at whole-chromosome and genome-wide levels. These studies have provided new insights into the mechanisms that influence origin selection and the temporally co-ordinated activation of replication initiation from these sites. Here we describe multiple microarray-based approaches that have been used to study DNA replication in both S. cerevisiae and higher eukaryotes. We have also compiled the data from the yeast microarray-based replication studies to generate a comprehensive list of origins that has been verified in three independent studies. The comprehensive nature of the microarray-based studies has revealed clear connections between chromosome organization and the pattern of replication. For example, in yeast, the centromeric proximal sequences are consistently early replicating and telomeric regions are consistently late replicating. The metazoan studies reveal a recurring theme of gene-dense transcriptionally active regions of the genome replicating before gene-sparse regions. In addition to the insights they have provided already, microarray-based replication assays combined with genetic analysis will provide a powerful new approach to define the mechanisms that regulate replication origin function.
DNA微阵列技术的最新进展使得真核生物复制能够在全染色体和全基因组水平上进行研究。这些研究为影响起始点选择的机制以及从这些位点进行的复制起始的时间协调激活提供了新的见解。在这里，我们描述了多种基于微阵列的方法，这些方法已被用于研究酿酒酵母和高等真核生物中的DNA复制。我们还汇总了基于酵母微阵列的复制研究数据，以生成一份在三项独立研究中得到验证的起始点综合列表。基于微阵列研究的全面性揭示了染色体组织与复制模式之间的明确联系。例如，在酵母中，着丝粒近端序列始终是早期复制的，而端粒区域始终是晚期复制的。后生动物研究揭示了一个反复出现的主题，即基因组中基因密集的转录活性区域先于基因稀疏区域进行复制。除了已经提供的见解之外，基于微阵列的复制测定与遗传分析相结合将为定义调节复制起始点功能的机制提供一种强大的新方法。
