REGULATION OF THE IPL1/SLI15 COMPLEX

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。染色体必须准确地分离到子细胞，以防止基因组不稳定和非整倍体，这是所有肿瘤的标志。染色体运动是通过微管和着丝粒相互作用产生的，着丝粒是聚集在着丝粒DNA上的特殊蛋白质复合体。准确的染色体分离依赖于姐妹着丝点的生物定向，使它们与来自相反纺锤体极点的微管结合。虽然Ipl1/Sli15复合体可以检测和纠正动粒双向缺陷，但目前还不清楚该复合体是如何受缺乏双向定向的影响的。Ipl1是一种由Sli15蛋白激活的蛋白激酶。因此，我们将通过FRET分析Ipl1和Sli15在动点上的相互作用，并测试这种相互作用是否会因双向的存在而改变。这些研究可能阐明有关Ipl1/Sli15复合体调控的重要细节。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chromosomes must accurately segregate to daughter cells to prevent genomic instability and aneuploidy, a hallmark of all tumors. Chromosome movements are generated through the interaction of microtubules with kinetochores, the specialized protein complexes that assemble on centromeric DNA. Accurate chromosome segregation depends on sister kinetochores biorienting such that they bind to microtubules arising from opposite spindle poles. Although the Ipl1/Sli15 complex detects and corrects defects in kinetochore biorientation, it is not clear how the complex is regulated by the presence of absence of biorientation. Ipl1 is a protein kinase that is activated by the Sli15 protein. We will therefore analyze the interaction between Ipl1 and Sli15 on kinetochores by FRET and test whether the interaction is altered by the presence or absence of biorientation. These studies may elucidate important details about the regulation of the Ipl1/Sli15 complex.