The control of chromosome structure by cohesin/condensin complexes

染色体分离不仅取决于微管提供的力，还取决于染色体形态的复杂控制。间期染色体在细胞核内占据一定的空间，姐妹染色单体在合成过程中相互连接(凝聚)，姐妹DNA序列在有丝分裂纺锤体上排列之前被包装成并列的圆柱体(凝聚)。凝聚和缩合都依赖于多亚单位复合体，分别是粘附素和缩合，它们包含杆状SMC蛋白，在每条臂的末端形成V形异二聚体和ABC样ATPase。SMC蛋白比核小体更古老，因为它们还控制着细菌类核的形态和分配。最近发现粘附素的Kleisin亚基连接着SMC异源二聚体的ATPase“头”，这表明粘附素可能通过将双螺旋捕获到一个巨大的蛋白质环中来发挥作用。我们建议研究SMC/Kleisin装置的分子性质及其对染色体形态的影响。后者将需要新的光和电子显微技术来探测染色体结构。我们的目标是解决是否所有的SMC/Kleisin装置都使用相同的基本原理，这个原理是什么，不同的装置如何导致染色体形态的不同方面，以及它们的活动在细胞周期中是如何调节的。

Chromosome segregation depends not only on forces provided by microtubules but also on the intricate control of chromosome morphology. Interphase chromosomes occupy defined spaces within the nucleus, sister chromatids are connected to each other during their synthesis (cohesion), and sister DNA sequences are packed into juxtaposed cyclindrical volumes (condensation) prior to their alignment on mitotic spindles. Both cohesion and condensation depend on multi-subunit complexes, cohesin and condensing respectively, which contain rod-shaped Smc proteins that form V-shaped hetero-dimers with ABC-like ATPases at the end of each arm. Smc proteins are more ancient than nucleosomes because they also control the morphology and partitioning of bacterial nucleoids. The recent finding that cohesin's kleisin subunit connects the ATPase "heads" of Smc heterodimers suggests that cohesin might operate by trapping double helices inside a huge proteinaceous ring. We propose to investigate the molecular properties of Smc/kleisin devices and their effects on chromosome morphology. The latter will require novel light and electron microsopic techniques to probe chromosome structure. We aim to address whether all Smc/kleisin devices operate using the same fundamental principle , what this principle is, how different devices lead to different aspects of chromosome morphology, and how their activities are regulated during the cell cycle.