p300/CREB-binding protein interacts with ATR and is required for the DNA replication checkpoint
p300/CREB-binding protein interacts with ATR and is required for the DNA replication checkpoint
复制标题
DOI：
10.1074/jbc.m609261200
复制
发表时间：
2007-03-30
影响因子：
4.8
通讯作者：
Thayer, Mathew
中科院分区：
文献类型：
--
作者：
Stauffer, Daniel;Chang, Bill;Thayer, Mathew
高度相关的乙酰转移酶、p300 和 CREB 结合蛋白 (CBP) 是信号响应转录激活的共激活因子。此外，最近的证据表明 p300/CBP 还与介导 DNA 复制和修复的复合物直接相互作用。在本报告中，我们表明哺乳动物细胞中 p300/CBP 的缺失会导致 DNA 复制停滞引起的细胞周期停滞缺陷。我们证明，可以在哺乳动物细胞中检测到包含 p300/CBP 和 ATR 的复合物，并且下游激酶 CHK1 无法响应缺乏 p300/CBP 的细胞中 DNA 复制停滞而被磷酸化。这些观察结果扩大了 p300/CBP 乙酰转移酶的作用，包括在 DNA 代谢事件以及转录过程中调节染色质结构和功能。
The highly related acetyltransferases, p300 and CREB-binding protein (CBP) are coactivators of signal-responsive transcriptional activation. In addition, recent evidence suggests that p300/CBP also interacts directly with complexes that mediate DNA replication and repair. In this report, we show that loss of p300/CBP in mammalian cells results in a defect in the cell cycle arrest induced by stalled DNA replication. We demonstrate that complexes containing p300/CBP and ATR can be detected in mammalian cells, and that the downstream kinase CHK1 fails to be phosphorylated in response to stalled DNA replication in cells that lack p300/CBP. These observations broaden the roles for the p300/CBP acetyltransferases to include the modulation of chromatin structure and function during DNA metabolic events as well as for transcription.