Benbow R M, Zhao J, Larson D D
Nucleic Acid Research Facility, Iowa State University, Ames 50011.
Bioessays. 1992 Oct;14(10):661-70. doi: 10.1002/bies.950141004.
Chromosomal origins of DNA replication in higher eukaryotes differ significantly from those of E. coli (oriC) and the tumor virus, SV40 (ori sequence). Initiation events appear to occur throughout broad zones rather than at specific origin sequences. Analysis of four chromosomal origin regions reveals that they share common modular sequence elements. These include DNA unwinding elements, pyrimidine tracts that may serve as strong DNA polymerase-primase start sites, scaffold associated regions, transcriptional regulatory sequences, and, possibly, initiator protein binding sites and inherently destabilized regions. Based on the novel organization of chromosomal origin regions, we propose a model for initiation of DNA replication in higher eukaryotes. Unwinding of duplex DNA during initiation may be uncoupled, both temporally and spatially, from DNA synthesis, resulting in transient single-stranded intermediates that function in lieu of conventional replication forks during chromosomal DNA replication. DNA synthesis begins subsequently at multiple sites within the unwound regions rather than at specific origin sequences.
高等真核生物中DNA复制的染色体起源与大肠杆菌（oriC）和肿瘤病毒SV40（ori序列）的染色体起源有显著差异。起始事件似乎发生在广泛的区域，而不是特定的起源序列处。对四个染色体起源区域的分析表明，它们共享共同的模块化序列元件。这些元件包括DNA解旋元件、可能作为强大的DNA聚合酶-引发酶起始位点的嘧啶序列、支架相关区域、转录调控序列，以及可能的起始蛋白结合位点和固有不稳定区域。基于染色体起源区域的新组织方式，我们提出了一个高等真核生物中DNA复制起始的模型。起始过程中双链DNA的解旋在时间和空间上可能与DNA合成解偶联，从而产生在染色体DNA复制过程中替代传统复制叉发挥作用的瞬时单链中间体。随后，DNA合成在解旋区域内的多个位点开始，而不是在特定的起源序列处。
