A role for a replicator dominance mechanism in silencing.
A role for a replicator dominance mechanism in silencing.
复制标题
复制子优势机制在沉默中的作用。
DOI：
10.1093/emboj/18.13.3808
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Fox,CA
中科院分区：
文献类型：
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作者：
PalaciosDeBeer,MA;Fox,CA
研究了天然HMR-E沉默因子在调控复制起始和起源识别复合体(ORC)沉默中的作用。当天然的hmr-E是唯一控制hmr的沉默因子时，沉默因子的ORC结合位点(Acs)对于复制的启动是必不可少的，这表明在其附近存在一个非沉默的染色体复制子(S)。进一步的分析表明，HMR-E两侧的区域含有复制子。在orc2-1突变体中，非沉默复制子(S)的复制启动被取消，这表明这些复制子对orc中的缺陷非常敏感。值得注意的是，其中一个非沉默复制子的活性与沉默减少相关；orc2-1突变或侧翼序列缺失导致的这些复制子的失活增强了沉默。这些数据与HMR-E沉默剂ACS结合的ORC在抑制邻近能够抑制沉默的ORC分子功能中的作用是一致的，并表明HMR自身ORC结合位点的差异对ORC功能有深刻的影响。此外，天然HMR-E的复制起始效率很低，这表明HMR内紧密分布的复制子有助于抑制复制起始。
The role of the natural HMR‐E silencer in modulating replication initiation and silencing by the origin recognition complex (ORC) was examined. When natural HMR‐E was the only silencer controlling HMR, the silencer's ORC‐binding site (ACS) was dispensable for replication initiation but essential for silencing, indicating that a non‐silencer chromosomal replicator (s) existed in close proximity to the silencer. Further analysis revealed that regions flanking both sides of HMR‐E contained replicators. In contrast to replication initiation by the intact silencer, initiation by the non‐silencer replicator (s) was abolished in an orc2‐1 mutant, indicating that these replicators were extremely sensitive to defects in ORC. Remarkably, the activity of one of the non‐silencer replicators correlated with reduced silencing; inactivation of these replicators caused by either the orc2‐1 mutation or the deletion of flanking sequences enhanced silencing. These data were consistent with a role for the ORC bound to the HMR‐E silencer ACS in suppressing the function of neighboring ORC molecules capable of inhibiting silencing, and indicated that differences in ORC‐binding sites within HMR itself had profound effects on ORC function. Moreover, replication initiation by natural HMR‐E was inefficient, suggesting that closely spaced replicators within HMR contributed to an inhibition of replication initiation.