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首页> 外文期刊>PLoS Genetics >The Origin Recognition Complex Interacts with a Subset of Metabolic Genes Tightly Linked to Origins of Replication
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The Origin Recognition Complex Interacts with a Subset of Metabolic Genes Tightly Linked to Origins of Replication

机译：起源识别复合体与紧密连接到复制起源的代谢基因子集相互作用

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The origin recognition complex (ORC) marks chromosomal sites as replication origins and is essential for replication initiation. In yeast, ORC also binds to DNA elements called silencers, where its primary function is to recruit silent information regulator (SIR) proteins to establish transcriptional silencing. Indeed, silencers function poorly as chromosomal origins. Several genetic, molecular, and biochemical studies of HMR-E have led to a model proposing that when ORC becomes limiting in the cell (such as in the orc2-1 mutant) only sites that bind ORC tightly (such as HMR-E) remain fully occupied by ORC, while lower affinity sites, including many origins, lose ORC occupancy. Since HMR-E possessed a unique non-replication function, we reasoned that other tight sites might reveal novel functions for ORC on chromosomes. Therefore, we comprehensively determined ORC “affinity” genome-wide by performing an ORC ChIP–on–chip in ORC2 and orc2-1 strains. Here we describe a novel group of orc2-1–resistant ORC–interacting chromosomal sites (ORF–ORC sites) that did not function as replication origins or silencers. Instead, ORF–ORC sites were comprised of protein-coding regions of highly transcribed metabolic genes. In contrast to the ORC–silencer paradigm, transcriptional activation promoted ORC association with these genes. Remarkably, ORF–ORC genes were enriched in proximity to origins of replication and, in several instances, were transcriptionally regulated by these origins. Taken together, these results suggest a surprising connection among ORC, replication origins, and cellular metabolism.
机译：起源识别复合体（ORC）将染色体位点标记为复制起源，并且对于复制启动至关重要。在酵母中，ORC还与称为沉默子的DNA元素结合，其主要功能是募集沉默信息调节剂（SIR）蛋白以建立转录沉默。实际上，消音器作为染色体起源的功能很差。 HMR-E的一些遗传学，分子学和生化研究已导致建立了一个模型，该模型提出当ORC在细胞中（例如orc2-1突变体）变得有限时，只有紧密结合ORC的位点（例如HMR-E）保留下来完全由ORC占用，而较低亲和力的站点（包括许多起源）会丢失ORC占用。由于HMR-E具有独特的非复制功能，我们认为其他紧密位点可能揭示了ORC在染色体上的新功能。因此，我们通过在ORC2和orc2-1菌株中进行芯片上的ORC ChIP芯片全面确定了ORC“全基因组”范围。在这里，我们描述了一组新的orc2-1抗性ORC相互作用的染色体位点（ORF–ORC位点），这些位点不能用作复制起点或沉默子。相反，ORF–ORC位点由高度转录的代谢基因的蛋白质编码区组成。与ORC-沉默子范式相反，转录激活促进了ORC与这些基因的缔合。值得注意的是，ORF–ORC基因在复制起点附近富集，并且在某些情况下受这些起点的转录调控。综上所述，这些结果表明，ORC，复制起点和细胞代谢之间存在令人惊讶的联系。

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