Analysis of the Topoisomerase II-Dependent Decatenation G2 Checkpoint and Checkpoint Kinases in Human Cells
Analysis of the Topoisomerase II-Dependent Decatenation G2 Checkpoint and Checkpoint Kinases in Human Cells
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DOI：
10.1007/978-1-60761-340-4_13
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发表时间：
2009-01-01
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影响因子：
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通讯作者：
Kaufmann, William K.
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文献类型：
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作者：
Kaufmann, William K.
使用毒物和催化抑制剂抑制Topo II功能触发检查点，其起到延迟G2细胞进入有丝分裂的进展的作用。Topo II毒素诱导Topo II相关的DNA双链断裂，激活ATM和DNA损伤G2检查点。拓扑异构酶II催化抑制剂不诱导DNA双链断裂，但阻断相互缠绕的子染色单体的解链。在有丝分裂后期前完全去连锁是染色单体分离所必需的。G2细胞似乎感觉到染色单体臂连接的程度，并通过持续抑制有丝分裂促进因子（MPF）和Polo样激酶I（Plk-1）激酶活性（通常推动G2细胞进入有丝分裂）来主动延迟有丝分裂的开始。本章详细介绍了检测去连环化G2检查点功能和检查点激酶活性的方法。
Inhibition of Topo II function using poisons and catalytic inhibitors triggers checkpoints that act to delay progression of G2 cells into mitosis. Topo II poisons induce Topo II-associated DNA double-strand breaks that activate ATM and the DNA damage G2 checkpoint. Topo II catalytic inhibitors do not induce DNA double-strand breaks but block decatenation of intertwined daughter chromatids. Complete decatenation before anaphase of mitosis is required for chromatid segregation. G2 cells appear to sense the degree of chromatid arm catenations and actively delay the onset of mitosis by sustaining the inhibition of mitosis-promoting factor (MPF) and polo-like kinase I (Plk-1) kinase activities that normally propel G2 cells into mitosis. This chapter details the methods for assay of decatenation G2 checkpoint function and checkpoint kinase activities.