在哺乳动物细胞中依赖拓酶II的G2循环检查点/
C S Downes1, D J Clarke, A M Mullinger
1Department of Zoology, University of Cambridge, UK.
Nature
|December 1, 1994
概括
在完整的染色体凝聚过程中,DNA拓聚酶II是至关重要的. 一个独特的连接敏感检查点调节细胞周期从G2退出,与DNA损伤控制分开.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- DNA拓酶II在复制过程中解决DNA链接,对染色体凝聚至关重要.
- 拓酶II抑制剂通常会在G2阶段因DNA损伤和检查点激活而阻止细胞.
- 拓聚酶II在G2/M进展中的确切作用和细胞周期检查点的存在仍在调查中.
研究的目的:
- 调查DNA拓酶II对于完整的染色体凝聚和细胞周期进展的必要性.
- 区分拓酶II活性和DNA损伤在G2/M细胞循环中所起的作用.
- 确定管理退出G2阶段的监管机制.
主要方法:
- 使用双二氧化,特别是ICRF-193,作为无损害DNA的二氧化酶II抑制剂.
- 雇佣了像咖啡因这样的避开检查站的代理来绕过G2的逮捕.
- 在哺乳动物细胞中观察到染色体凝聚和细胞周期进展.
主要成果:
- ICRF-193 阻断了进入线粒分裂的过程,但未能从G2中退出,这表明了拓酶II在最初的线粒细胞进入之后的作用.
- 避开检查点的药物诱导了流产性染色体凝结,证实了拓酶II对完全凝结的要求.
- 证明G2出口由连锁敏感检查点控制,独立于G2损坏检查点.
结论:
- 对于实现完全凝聚的染色体而言,DNA拓酶II是必不可少的.
- 一个新的连锁敏感检查点机制调节了G2阶段的进展.
- 这个连锁敏感的检查点与已建立的G2损坏检查点路径不同.
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