Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Mol Biol Cell. 2010 Apr 1;21(7):1188-99. doi: 10.1091/mbc.e09-11-0950. Epub 2010 Feb 3.
To maintain genomic stability, chromosome architecture needs to be tightly regulated as chromosomes undergo condensation during prophase and separation during anaphase, but the mechanisms remain poorly understood. Here, we show that the Plk1-binding protein PICH and Plk1 kinase coordinately maintain chromosome architecture during prometaphase. PICH knockdown results in a loss of Plk1 from the chromosome arm and an increase in highly disorganized "wavy" chromosomes that exhibit an "open" or "X-shaped" configuration, consistent with a loss of chromosome arm cohesion. Such chromosome disorganization occurs with essentially no change in the localization of condensin or cohesin on chromosomes. Interestingly, the chromosome disorganization could be prevented by treatment with a topoisomerase II inhibitor ICRF-193, suggesting that the PICH-Plk1 complex normally maintains chromosome architecture in a manner that involves topoisomerase II activity. PICH knockdown does not affect initial chromosome compaction at prophase but causes anaphase DNA bridge formation and failed abscission. Our studies suggest that the PICH-Plk1 complex plays a critical role in maintaining prometaphase chromosome architecture.
为了维持基因组的稳定性，染色体结构需要在前期进行浓缩和后期进行分离时受到严格的调控，但调控机制仍知之甚少。在这里，我们发现 Plk1 结合蛋白 PICH 和 Plk1 激酶在前期协同维持染色体结构。PICH 敲低导致 Plk1 从染色体臂上丢失，并增加高度紊乱的“波浪状”染色体，表现出“开放”或“X 形”的结构，这与染色体臂内聚力的丧失一致。这种染色体的紊乱发生在染色体上的凝聚蛋白或黏连蛋白的定位基本没有变化的情况下。有趣的是，用拓扑异构酶 II 抑制剂 ICRF-193 处理可以防止染色体的紊乱，这表明 PICH-Plk1 复合物通常以涉及拓扑异构酶 II 活性的方式维持染色体结构。PICH 敲低不影响前期的染色体初始浓缩，但导致后期 DNA 桥的形成和分裂失败。我们的研究表明，PICH-Plk1 复合物在维持前期染色体结构方面起着关键作用。
