An ARS element inhibits DNA replication through a SIR2-Dependent mechanism
An ARS element inhibits DNA replication through a SIR2-Dependent mechanism
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DOI：
10.1016/j.molcel.2008.02.019
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发表时间：
2008-04-25
期刊：
影响因子：
16
通讯作者：
Weinreich, Michael
中科院分区：
文献类型：
--
作者：
Crampton, Amber;Chang, FuJung;Weinreich, Michael
在G1期，决定DNA合成起始位置的复制前复合物（pre-RC）在起源处形成。Sir 2 p组蛋白去乙酰化酶抑制在一个子集的起源前RC组装，表明Sir 2 p，抑制DNA复制通过一个独特的方面的起源结构。在这里，我们确定了五个SIR 2敏感的起源染色体III和VI。两个起源的连接子扫描分析表明，它们共享一个共同的组织，包括位于起源识别复合物（ORC）结合和前RC组装位点3'的抑制序列。该抑制序列（I-s）需要SIR 2来实现其活性，表明SIR 2通过该序列抑制起源。此外，Is元件发生在定位的核小体内，并且Abf 1 p介导的从原点排除核小体废除了抑制。这些数据表明，Sir 2 p和Is元件通过促进对前RC组装不利的染色质结构来抑制起源活性。
During G1 phase, a prereplicative complex (pre-RC) that determines where DNA synthesis initiates forms at origins. The Sir2p histone deacetylase inhibits pre-RC assembly at a subset of origins, suggesting that Sir2p, inhibits DNA replication through a unique aspect of origin structure. Here, we identified five SIR2-sensitive origins on chromosomes III and VI . Linker scan analysis of two origins indicated that they share a common organization, including an inhibitory sequence positioned 3' to the sites of origin recognition complex (ORC) binding and pre-RC assembly. This inhibitory sequence (I-s) required SIR2 for its activity, suggesting that SIR2 inhibits origins through this sequence. Furthermore, Is elements occurred within positioned nucleosomes, and Abf1 p-mediated exclusion of nucleosomes from the origin abrogated the inhibition. These data suggest that Sir2p, and Is elements inhibit origin activity by promoting an unfavorable chromatin structure for pre-RC assembly.