DNA topoisomerase IIα interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution
DNA topoisomerase IIα interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution
复制标题
DOI：
10.1016/s0960-9822(00)00620-5
复制
发表时间：
2000-07-27
期刊：
影响因子：
9.2
通讯作者：
Earnshaw, WC
中科院分区：
文献类型：
--
作者：
Durrieu, F;Samejima, K;Earnshaw, WC
凋亡执行的特征是核结构的急剧变化伴随着caspase对核蛋白的切割(综述在[1]中)，无细胞提取物已被证明有助于鉴定参与凋亡执行的活性[2-4]和鉴定被caspase切割的蛋白质[5]，最近的研究表明，核的分解主要是由caspase下游激活的因子驱动的[6]，其中一个这样的因子，caspase激活的DNA酶，CAD/CPAN/DFF40[4，7，8](CAD)可以在没有其他细胞因子的情况下诱导HeLa细胞核发生染色质凝聚[6，8]然而，由于即使在抑制CAD活性的情况下也会发生染色质凝聚，CAD不是caspase[6]触发的唯一形态发生因子，因此我们在这里展示了DNA拓扑异构酶Ha(Topo IIα)，它在有丝分裂中对子染色体的凝聚和分离是必不可少的[9]，也在凋亡执行过程中发挥作用。同时抑制Topo IIα和半胱氨酸天冬氨酸氨基转移酶可完全消除凋亡的染色质凝聚。此外，我们还证明了CAD与Topo IIα结合，并且它们的结合在体外增强了Topo IIα的杀菌活性，(C)2000爱思唯尔科学有限公司。保留所有权利。
Apoptotic execution is characterized by dramatic changes in nuclear structure accompanied by cleavage of nuclear proteins by caspases (reviewed in [1]), Cell free extracts have proved useful for the identification and functional characterization of activities involved in apoptotic execution [2-4] and for the identification of proteins cleaved by caspases [5], More recent studies have suggested that nuclear disassembly is driven largely by factors activated downstream of caspases [6], One such factor, the caspase-activated DNase, CAD/CPAN/DFF40 [4,7,8] (CAD) can induce apoptotic chromatin condensation in isolated HeLa cell nuclei in the absence of other cytosolic factors [6,8], As chromatin condensation occurs even when CAD activity is inhibited, however, CAD cannot be the sole morphogenetic factor triggered by caspases [6], Here we show that DNA topoisomerase Ha (Topo II alpha), which is essential for both condensation and segregation of daughter chromosomes in mitosis [9], also functions during apoptotic execution. Simultaneous inhibition of Topo II alpha and caspases completely abolishes apoptotic chromatin condensation. In addition, we show that CAD binds to Topo II alpha, and that their association enhances the decatenation activity of Topo II alpha in vitro, (C) 2000 Elsevier Science Ltd. All rights reserved.