IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal.
J Cell Sci. 2012 Feb 1;125(Pt 3):576-83. doi: 10.1242/jcs.092445.
Correct chromosome segregation during cell division requires bi-orientation at the mitotic spindle. Cells possess mechanisms to prevent and correct inappropriate chromosome attachment. Sister kinetochores assume a 'back-to-back' geometry on chromosomes that favors amphitelic orientation but the regulation of this process and molecular components are unknown. Abnormal chromosome-spindle interactions do occur but are corrected through the activity of Aurora B, which destabilizes erroneous attachments. Here, we address the role of Drosophila POLO in chromosome-spindle interactions and show that, unlike inhibition of its activity, depletion of the protein results in bipolar spindles with most chromosomes forming stable attachments with both sister kinetochores bound to microtubules from the same pole in a syntelic orientation. This is partly the result of impaired localization and activity of Aurora B but also of an altered centromere organization with abnormal distribution of centromeric proteins and shorter interkinetochore distances. Our results suggests that POLO is required to promote amphitelic attachment and chromosome bi-orientation by regulating both the activity of the correction mechanism and the architecture of the centromere.
正确的染色体分离需要在有丝分裂纺锤体中进行双定向。细胞具有防止和纠正不当染色体附着的机制。姐妹动粒在染色体上呈现出“背靠背”的几何形状，有利于合极性取向，但这个过程的调节和分子成分尚不清楚。异常的染色体-纺锤体相互作用确实会发生，但通过 Aurora B 的活性得到纠正，Aurora B 会使错误的连接不稳定。在这里，我们研究了果蝇 POLO 在染色体-纺锤体相互作用中的作用，并表明与抑制其活性不同，耗尽该蛋白会导致两极纺锤体形成稳定的附着，两个姐妹动粒都与来自同一极的微管结合，呈合极性取向。这部分是由于 Aurora B 的定位和活性受损，但也与着丝粒组织的改变有关，表现为着丝粒蛋白的异常分布和动粒间距离缩短。我们的结果表明，POLO 通过调节校正机制的活性和着丝粒的结构，促进合极性附着和染色体双定向。
