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首页> 外文期刊>Molecular and Cellular Biology >The Human β-Globin Replication Initiation Region Consists of Two Modular Independent Replicators
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The Human β-Globin Replication Initiation Region Consists of Two Modular Independent Replicators

机译：人β-球蛋白复制起始区由两个模块化独立复制子组成

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Previous studies have shown that mammalian cells contain replicator sequences, which can determine where DNA replication initiates. However, the specific sequences that confer replicator activity were not identified. Here we report a detailed analysis of replicator sequences that dictate initiation of DNA replication from the human β-globin locus. This analysis suggests that the β-globin replication initiation region contains two adjacent, redundant replicators. Each replicator was capable of initiating DNA replication independently at ectopic sites. Within each of these two replicators, we identified short, discrete, nonredundant sequences, which cooperatively determine replicator activity. Experiments with somatic cell hybrids further demonstrated that the requirements for initiation at ectopic sites were similar to the requirements for initiation within native human chromosomes. The replicator clustering and redundancy exemplified in the human β-globin locus may account for the extreme difficulty in identifying replicator sequences in mammalian cells and suggest that mammalian replication initiation sites may be determined by cooperative sequence modules.
机译：先前的研究表明，哺乳动物细胞包含复制子序列，该序列可以确定DNA复制的起始位置。但是，未鉴定到赋予复制子活性的特定序列。在这里，我们报告了详细的复制子序列分析，这些序列决定了从人β-珠蛋白基因座开始DNA复制的过程。该分析表明，β-珠蛋白复制起始区包含两个相邻的冗余复制子。每个复制子都能够独立地在异位点启动DNA复制。在这两个复制子的每一个中，我们鉴定了短的，离散的，非冗余的序列，它们共同决定了复制子的活性。体细胞杂种的实验进一步证明，在异位点启动的要求类似于在天然人类染色体内启动的要求。人β-珠蛋白基因座中举例说明的复制子聚类和冗余可能解释了鉴定哺乳动物细胞中复制子序列的极端困难，并表明哺乳动物复制起始位点可以由协同序列模块确定。

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