DIFFERENTIAL EXPRESSION OF DNA TOPOISOMERASES-I AND TOPOISOMERASES-II DURING THE EUKARYOTIC CELL-CYCLE
DIFFERENTIAL EXPRESSION OF DNA TOPOISOMERASES-I AND TOPOISOMERASES-II DURING THE EUKARYOTIC CELL-CYCLE
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DOI：
10.1073/pnas.85.4.1086
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发表时间：
1988-02-01
影响因子：
11.1
通讯作者：
EARNSHAW, WC
中科院分区：
文献类型：
--
作者：
HECK, MMS;HITTELMAN, WN;EARNSHAW, WC
我们利用抗体探针来检测正常细胞和转化细胞中 DNA 拓扑异构酶 I 和 II 以及染色体支架蛋白 Sc-2 的表达。拓扑异构酶 I 和 Sc-2 在整个细胞周期中的含量或稳定性均未表现出显着波动。相比之下，拓扑异构酶 II 在数量和稳定性方面都经历了显着的细胞周期依赖性改变。当细胞从有丝分裂进入 G1 期时，大部分拓扑异构酶 II 被降解。在 G1 的前 2 小时内，拓扑异构酶 II 的半衰期比异步细胞群中测量的半衰期缩短了 7 倍。这表明染色体缩合/解缩循环与拓扑异构酶 II 的合成和降解的平行循环耦合。在对照实验中，我们还发现正常细胞中拓扑异构酶 II 的半衰期比转化细胞短 4 倍。由于正常细胞中每个细胞的拓扑异构酶 II 拷贝数也较低，这表明拓扑异构酶 II 稳定性的控制在转化后发生了改变。拓扑异构酶 I 和 Sc-2 的稳定性在正常细胞和转化细胞之间没有显着差异。
We have utilized antibody probes to examine the expression of DNA topoisomerases I and II and chromosome scaffold protein Sc-2 in normal and transformed cells. Neither topoisomerase I nor Sc-2 shows significant fluctuations in content or stability across the cell cycle. In contrast, topoisomerase II undergoes significant cell cycle-dependent alterations in both amount and stability. As cells progress from mitosis into G1, much of the topoisomerase II is degraded. During the first 2 hr of G1, the half life of topoisomerase II is decreased from that measured in asynchronous cell populations by a factor of 7. This suggests that the chromosome condensation/decondensation cycle is coupled to a parallel cycle of synthesis and degradation of topoisomerase II. In control experiments, we also found that the half-life of topoisomerase II is shorter in normal cells than in transformed cells by a factor of 4. Since the number of copies of topoisomerase II per cell is also lower in normal cells, this suggests that control of topoisomerase II stability is altered upon transformation. The stability of topoisomerase I and Sc-2 does not differ significantly between normal and transformed cells.