DNA replication

Studies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyces cerevisiae (budding yeast), is well understood, and has served as a model for studies of DNA replication initiation in multicellular eukaryotes, including humans. In general terms, the first step of initiation is the binding of the replication initiator to the origin of replication. The replicative helicase is then assembled onto the origin, usually by a helicase assembly factor. Either shortly before or shortly after helicase assembly, some local unwinding of the origin of replication occurs in a region rich in adenine and thymine bases (often termed a DNA unwinding element, DUE). The unwound region provides the substrate for primer synthesis and initiation of DNA replication. The best-defined eukaryotic origins are those of S. cerevisiae, which have well-conserved sequence elements for initiator binding, DNA unwinding and binding of accessory proteins. In multicellular eukaryotes, unlike S. cerevisiae, these loci appear not to be defined by the presence of a DNA sequence motif. Indeed, choice of replication origins in a multicellular eukaryote may vary with developmental stage and tissue type. In cell-free models of metazoan DNA replication, such as the one provided by Xenopus egg extracts, there are only limited DNA sequence specificity requirements for replication initiation. Source description: http://www.reactome.org/content/detail/69306.

近十年来，研究指出生命各界的DNA复制起始机制得以保留。在单细胞真核生物，尤其是酿酒酵母（出芽酵母）中的起始机制已被深入研究，并成为多细胞真核生物，包括人类在内，DNA复制起始研究的模型。概而言之，起始的第一步是复制起始因子与复制起点结合。随后，复制的解旋酶组装到起点上，通常由解旋酶组装因子实现。解旋酶组装之前或之后不久，在富含腺嘌呤和胸腺嘧啶碱基的区域（常称为DNA解旋元件，DUE）发生局部解旋。解旋的区段为引物合成和DNA复制起始提供了底物。定义最为明确的真核生物起源当属酿酒酵母，其具有高度保守的起始因子结合、DNA解旋及辅助蛋白结合的序列元件。在多细胞真核生物中，与酿酒酵母不同，这些位点似乎并非由DNA序列模式的存在来界定。实际上，在多细胞真核生物中，复制起点的选择可能随着发育阶段和组织类型的差异而变化。在无细胞模型中，如由非洲爪蟾卵提取物提供的真核生物DNA复制模型，复制起始仅对DNA序列具有有限的特异性要求。源描述：http://www.reactome.org/content/detail/69306.