DNA replication origins-where do we begin?

In this review, Prioleau and MacAlpine summarize recent advances in our understanding of how primary sequence, chromatin environment, and nuclear architecture contribute to the dynamic selection and activation of replication origins across diverse cell types and developmental stages. For more than three decades, investigators have sought to identify the precise locations where DNA replication initiates in mammalian genomes. The development of molecular and biochemical approaches to identify start sites of DNA replication (origins) based on the presence of defining and characteristic replication intermediates at specific loci led to the identification of only a handful of mammalian replication origins. The limited number of identified origins prevented a comprehensive and exhaustive search for conserved genomic features that were capable of specifying origins of DNA replication. More recently, the adaptation of origin-mapping assays to genome-wide approaches has led to the identification of tens of thousands of replication origins throughout mammalian genomes, providing an unprecedented opportunity to identify both genetic and epigenetic features that define and regulate their distribution and utilization. Here we summarize recent advances in our understanding of how primary sequence, chromatin environment, and nuclear architecture contribute to the dynamic selection and activation of replication origins across diverse cell types and developmental stages.

在这篇综述中，普里奥洛（Prioleau）和麦卡尔平（MacAlpine）总结了我们在理解一级序列、染色质环境以及核结构如何在不同细胞类型和发育阶段对复制起点的动态选择和激活起作用方面的最新进展。 三十多年来，研究人员一直试图确定DNA复制在哺乳动物基因组中起始的确切位置。基于在特定位点存在明确且具有特征的复制中间体来鉴定DNA复制起始位点（起点）的分子和生化方法的发展，仅导致了少数哺乳动物复制起点的鉴定。已鉴定的起点数量有限，阻碍了对能够确定DNA复制起点的保守基因组特征进行全面而详尽的搜索。最近，将起点定位分析方法应用于全基因组范围的研究，已经在整个哺乳动物基因组中鉴定出数以万计的复制起点，为鉴定定义和调控其分布及利用的遗传和表观遗传特征提供了前所未有的机会。在此我们总结在理解一级序列、染色质环境以及核结构如何在不同细胞类型和发育阶段对复制起点的动态选择和激活起作用方面的最新进展。