The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks
The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks
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DOI：
10.1016/s0092-8674(04)00206-5
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发表时间：
2004-04-02
期刊：
影响因子：
64.5
通讯作者：
Caldecott, KW
中科院分区：
文献类型：
--
作者：
Loizou, JI;El-Khamisy, SF;Caldecott, KW
CK2是第一个被发现的蛋白激酶，是哺乳动物细胞增殖和存活所必需的。在这里，我们发现了CK2的一个意想不到的作用。我们发现这种必需的蛋白激酶磷酸化支架蛋白XRCC1，从而使DNA单链断裂修复蛋白复合物在体外和染色体断裂位点的组装和活性成为可能。此外，我们发现通过突变CK2磷酸化位点来抑制XRCC1的磷酸化，或使用高度特异性的抑制剂来阻止CK2的活性，会破坏XRCC1对细胞DNA单链断裂的快速修复。这些数据确定了CK2在染色体DNA链断裂修复和维持遗传完整性中的直接作用。
CK2 was the first protein kinase identified and is required for the proliferation and survival of mammalian cells. Here, we have identified an unanticipated role for CK2. We show that this essential protein kinase phosphorylates the scaffold protein XRCC1 and thereby enables the assembly and activity of DNA single-strand break repair protein complexes in vitro and at sites of chromosomal breakage. Moreover, we show that inhibiting XRCC1 phosphorylation by mutation of the CK2 phosphorylation sites or preventing CK2 activity using a highly specific inhibitor ablates the rapid repair of cellular DNA single-strand breaks by XRCC1. These data identify a direct role for CK2 in the repair of chromosomal DNA strand breaks and in maintaining genetic integrity.