INHIBITORS OF DNA TOPOISOMERASE-II PREVENT CHROMATID SEPARATION IN MAMMALIAN-CELLS BUT DO NOT PREVENT EXIT FROM MITOSIS
INHIBITORS OF DNA TOPOISOMERASE-II PREVENT CHROMATID SEPARATION IN MAMMALIAN-CELLS BUT DO NOT PREVENT EXIT FROM MITOSIS
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DOI：
10.1073/pnas.88.20.8895
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发表时间：
1991-10-01
影响因子：
11.1
通讯作者：
JOHNSON, RT
中科院分区：
文献类型：
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作者：
DOWNES, CS;MULLINGER, AM;JOHNSON, RT
DNA拓扑异构酶II(EC5.99.1.3)是酵母染色体凝聚和分离所必需的，但不是其他功能所必需的。在哺乳动物细胞中，据报道，它是有丝分裂进程所必需的，但不是通过有丝分裂传递所必需的。相反，我们发现，对拓扑异构酶II(而不是拓扑异构酶I)的特异性抑制干扰了哺乳动物的有丝分裂进程。在给予高浓度拓扑异构酶II抑制剂的细胞中，中期延长，染色单体后期分离完全被抑制；然而，这些细胞试图分裂，有时产生有核和无核的子体。较低浓度的抑制剂会干扰后期，并产生异常的分离。因此，DNA拓扑异构酶II的活性对于哺乳动物染色单体的分离是必要的，但它与其他有丝分裂事件的控制并不紧密相连。
DNA topoisomerase II (EC 5.99.1.3) is necessary for chromosome condensation and disjunction in yeast but not for other functions. In mammalian cells, it has been reported to be necessary for progression toward mitosis but not for transit through mitosis. We have found, on the contrary, that specific inhibition of topoisomerase II (but not of topoisomerase I) interferes with mammalian mitotic progression. Metaphase is prolonged, and anaphase separation of chromatids is completely inhibited, in cells given high concentrations of topoisomerase II inhibitors; nevertheless these cells attempt cleavage, sometimes generating nucleate and anucleate daughters. Lower concentrations of inhibitors interfere with anaphase and produce abnormalities of segregation. DNA topoisomerase II activity is therefore necessary for mammalian chromatid separation, but it is not tightly coupled to the control of other mitotic events.