Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry.
Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry.
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DOI：
10.1091/mbc.e11-10-0832
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发表时间：
2012-03
影响因子：
3.3
通讯作者：
Sullivan W
中科院分区：
文献类型：
--
作者：
Fasulo B;Koyama C;Yu KR;Homola EM;Hsieh TS;Campbell SD;Sullivan W
发现了新的染色体凝聚检查点。s期和拓扑异构酶抑制剂延缓染色体凝聚。这些延迟需要chk1和wee1。在中期板上引起染色体凝聚/聚合缺陷的抑制剂延缓了后期的进入。Wee1而不是主轴装配检查点介导延迟。DNA复制缺陷和染色体凝聚是肿瘤细胞常见的表型。复制和凝聚之间的联系已经建立，但很少知道检查点在监测染色体凝聚中的作用。我们利用早期果蝇胚胎的快速分裂周期，通过活体分析来研究这一功能。我们发现s期和拓扑异构酶抑制剂延缓了染色体凝聚的起始和速率。这些细胞周期延迟是由细胞周期激酶chk1和wee1介导的。在染色体凝聚和中期板上聚集时引起严重缺陷的抑制剂导致晚期进入延迟。这些延迟是由wee1介导的，而不是纺锤体组装检查点激活的结果。此外，我们首次提供了广泛使用的抗癌药物（阿克柔比星、ICRF-193、VM26、阿克柔比星、喜树碱、阿菲霉素、羟基脲、顺铂、氯胺嘧啶和x射线）对关键核和细胞质细胞周期事件的直接影响的详细现场分析。
New chromosome condensation checkpoints are identified. S-phase and topoisomerase inhibitors delay chromosome condensation. These delays require chk1 and wee1. Inhibitors causing defects in chromosome condensation/congression on the metaphase plate delay anaphase entry. wee1 and not the spindle assembly checkpoint mediates the delay. Defects in DNA replication and chromosome condensation are common phenotypes in cancer cells. A link between replication and condensation has been established, but little is known about the role of checkpoints in monitoring chromosome condensation. We investigate this function by live analysis, using the rapid division cycles in the early Drosophila embryo. We find that S-phase and topoisomerase inhibitors delay both the initiation and the rate of chromosome condensation. These cell cycle delays are mediated by the cell cycle kinases chk1 and wee1. Inhibitors that cause severe defects in chromosome condensation and congression on the metaphase plate result in delayed anaphase entry. These delays are mediated by wee1 and are not the result of spindle assembly checkpoint activation. In addition, we provide the first detailed live analysis of the direct effect of widely used anticancer agents (aclarubicin, ICRF-193, VM26, doxorubicin, camptothecin, aphidicolin, hydroxyurea, cisplatin, mechlorethamine and x-rays) on key nuclear and cytoplasmic cell cycle events.