A TOPOISOMERASE II-DEPENDENT G2 CYCLE CHECKPOINT IN MAMMALIAN-CELLS
A TOPOISOMERASE II-DEPENDENT G2 CYCLE CHECKPOINT IN MAMMALIAN-CELLS
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DOI：
10.1038/372467a0
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发表时间：
1994-12-01
期刊：
影响因子：
64.8
通讯作者：
JOHNSON, RT
中科院分区：
文献类型：
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作者：
DOWNES, CS;CLARKE, DJ;JOHNSON, RT
DNA拓扑异构酶II是酵母(3)和非洲爪哇提取物(4-6)中染色体凝聚所必需的，它消除了复制过程中姐妹染色单体DNA分子之间形成的连接(1)，是染色体核心的结构成分(2)。拓扑异构酶II的抑制剂在细胞周期的G2期有丝分裂之前阻止哺乳动物细胞(7)，但也会产生DNA损伤，这通过建立检查点控制而导致停止(8)。细胞是否需要拓扑异构酶II来离开G2，或者是否需要控制其活性来控制周期后期的进展，这是一个值得商榷的问题。双氧哌嗪是一种拓扑异构酶II抑制剂，作用不会造成直接的DNA损伤(9)；最有效的ICRF-193可以阻止哺乳动物进入有丝分裂，但不会退出有丝分裂。在这里，我们证明了像咖啡因这样的检查点逃避剂覆盖了这一障碍，产生了流产的浓缩染色体，这表明拓扑异构酶II是完全浓缩所必需的。我们发现，从G2退出是由一种连锁敏感的检查点机制来调节的，这与G2损害检查点不同。
THE enzyme DNA topoisomerase II, which removes the catenations formed between the DNA molecules of sister chromatids during replication(1) and is a structural component of chromosome cores(2), is needed for chromosome condensation in yeast(3) and in Xenopus extracts(4-6). Inhibitors of topoisomerase II arrest mammalian cells before mitosis in the G2 phase of the cell cycle(7), but also produce DNA damage, which causes arrest through established checkpoint controls(8). It is open to question whether cells need topoisomerase II to leave G2, or control late-cycle progression in response to its activity. Bisdioxopiperazines are topoisomerase II inhibitors that act without producing direct DNA damage(9); the most potent, ICRF-193, blocks mammalian entry into but not exit from mitosis. Here we show that checkpoint-evading agents such as caffeine override this block to produce abortively condensed chromosomes, indicating that topoisomerase II is needed for complete condensation. We find that exit from G2 is regulated by a catenation-sensitive checkpoint mechanism which is distinct from the G2-damage checkpoint.