ORIGIN RECOGNITION COMPLEX (ORC) IN TRANSCRIPTIONAL SILENCING AND DNA-REPLICATION IN SACCHAROMYCES-CEREVISIAE
ORIGIN RECOGNITION COMPLEX (ORC) IN TRANSCRIPTIONAL SILENCING AND DNA-REPLICATION IN SACCHAROMYCES-CEREVISIAE
复制标题
DOI：
10.1126/science.8266071
复制
发表时间：
1993-12-17
期刊：
影响因子：
56.9
通讯作者：
RINE, J
中科院分区：
文献类型：
--
作者：
FOSS, M;MCNALLY, FJ;RINE, J
在酿酒酵母中，HMR-E 沉默子阻断沉默子附近的蛋白质与其识别序列之间的位点特异性相互作用。沉默子功能与 HMR-E 复制起点的激发相关。通过筛选影响 HMR 表达的突变，鉴定出在转录沉默中发挥作用的重要基因。这个被称为 ORC2 的基因被证明可以编码结合酵母复制起点的起点识别复合物的一个组成部分。 ORC2 中的温度敏感突变破坏了在允许温度下生长的细胞的沉默。在限制温度下，orc2-1 突变导致细胞周期停滞在细胞周期的某个点，表明 DNA 复制受阻。 orc2-1突变还导致质粒有丝分裂损失增加，提示复制缺陷。这些结果为 ORC 在染色体复制和沉默中的体内作用提供了强有力的证据，并提供了沉默机制和 DNA 复制之间的联系。
In Saccharomyces cerevisiae, the HMR-E silencer blocks site-specific interactions between proteins and their recognition sequences in the vicinity of the silencer. Silencer function is correlated with the firing of an origin of replication at HMR-E. An essential gene with a role in transcriptional silencing was identified by means of a screen for mutations affecting expression of HMR. This gene, known as ORC2, was shown to encode a component of the origin recognition complex that binds yeast origins of replication. A temperature-sensitive mutation in ORC2 disrupted silencing in cells grown at the permissive temperature. At the restrictive temperature, the orc2-1 mutation caused cell cycle arrest at a point in the cell cycle indicative of blocks in DNA replication. The orc2-1 mutation also resulted in the enhanced mitotic loss of a plasmid, suggestive of a defect in replication. These results provide strong evidence for an in vivo role of ORC in both chromosomal replication and silencing, and provide a link between the mechanism of silencing and DNA replication.