Activation of the DNA replication checkpoint through RNA synthesis by primase
Activation of the DNA replication checkpoint through RNA synthesis by primase
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DOI：
10.1126/science.289.5487.2133
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发表时间：
2000-09-22
期刊：
影响因子：
56.9
通讯作者：
Newport, J
中科院分区：
文献类型：
--
作者：
Michael, WM;Ott, R;Newport, J
当DNA复制在细胞周期的合成（S）期被抑制时，信号传导途径（检查点）被激活，其用于防止有丝分裂在复制完成之前开始。该复制检查点通过下调有丝分裂诱导剂cdc 2-细胞周期蛋白B的活性而起作用。在这里，我们报告染色质结构和复制检查点的诱导之间的关系。染色质只有在DNA解绕和DNA聚合酶加载后才能启动检查点反应。检查点诱导不需要在解绕的模板链上合成新的DNA，但确实需要通过引发酶合成RNA引物。这些发现将引物的RNA部分鉴定为激活复制检查点的信号的重要组成部分。
When DNA replication is inhibited during the synthesis (S) phase of the cell cycle, a signaling pathway (checkpoint) is activated that serves to prevent mitosis from initiating before completion of replication. This replication checkpoint acts by down-regulating the activity of the mitotic inducer cdc2-cyclin B. Here, we report the relation between chromatin structure and induction of the replication checkpoint. Chromatin was competent to initiate a checkpoint response only after the DNA was unwound and DNA polymerase or had been Loaded. Checkpoint induction did not require new DNA synthesis on the unwound template strand but did require RNA primer synthesis by primase. These findings Identify the RNA portion of the primer as an important component of the signal that activates the replication checkpoint.