Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
Adv Exp Med Biol. 2017;1042:43-59. doi: 10.1007/978-981-10-6955-0_2.
In eukaryotes, genome duplication starts concomitantly at many replication initiation sites termed replication origins. The replication initiation program is spatially and temporally coordinated to ensure accurate, efficient DNA synthesis that duplicates the entire genome while maintaining other chromatin-dependent functions. Unlike in prokaryotes, not all potential replication origins in eukaryotes are needed for complete genome duplication during each cell cycle. Instead, eukaryotic cells vary the use of initiation sites so that only a fraction of potential replication origins initiate replication each cell cycle. Flexibility in origin choice allows each eukaryotic cell type to utilize different initiation sites, corresponding to unique nuclear DNA packaging patterns. These patterns coordinate replication with gene expression and chromatin condensation. Budding yeast replication origins share a consensus sequence that marks potential initiation sites. Metazoan origins, on the other hand, lack a consensus sequence. Rather, they are associated with a collection of structural features, chromatin packaging features, histone modifications, transcription, and DNA-DNA/DNA-protein interactions. These features confer cell type-specific replication and expression and play an essential role in maintaining genomic stability.
在真核生物中，基因组复制同时从许多称为复制起点的复制起始位点开始。复制起始程序在空间和时间上协调一致，以确保准确、高效的 DNA 合成，复制整个基因组，同时保持其他依赖染色质的功能。与原核生物不同，在真核生物中，并非所有潜在的复制起点都需要在每个细胞周期中完成整个基因组的复制。相反，真核细胞改变起始位点的使用，使得每个细胞周期只有一部分潜在的复制起点启动复制。起源选择的灵活性使每种真核细胞类型都能利用不同的起始位点，对应于独特的核 DNA 包装模式。这些模式与基因表达和染色质凝聚相协调。芽殖酵母复制起点具有标记潜在起始位点的一致序列。另一方面，后生动物起源缺乏一致序列。相反，它们与一系列结构特征、染色质包装特征、组蛋白修饰、转录和 DNA-DNA/DNA-蛋白质相互作用相关联。这些特征赋予细胞类型特异性的复制和表达，并在维持基因组稳定性方面发挥着重要作用。
