Identification of Yeast Chromosome Condensation Factors

描述（由申请人提供）解除染色体精确分离所需因素的管制可能导致非整倍体，这是癌症病因学的重要因素。复制基因组的平等分裂要求姐妹染色单体在有丝分裂后期迁移到纺锤体的相反两极：分离的保真度依赖于复杂的机制，并依赖于适当的染色体组织。参与染色体凝聚和基因组组织的因素也对维持基因组的稳定性至关重要。总之，基因组不稳定性和非整倍体是恶性进展的关键因素。参与染色体结构的已知蛋白质在人类和芽殖酵母（酿酒酵母）之间是高度保守的。然而，这些过程中涉及的许多因素仍有待分离。由于酵母在遗传上是易处理的，它们提供了理想的系统，其中可以快速识别细胞过程所需的新因素。我们的目标是鉴定和了解新的出芽酵母蛋白，通过细胞周期控制染色体组织和结构的动态。我们的假设是，这些蛋白质的人类同源物将需要维持染色体分离的保真度和基因组的完整性。因此，这些因素将与癌症的病因有关。

DESCRIPTION (provided by applicant) Deregulation of factors needed for accurate chromosome segregation can result in aneuploidy, a significant contributor to cancer etiology. Equal division of a replicated genome requires that sister chromatids migrate to opposite poles of the mitotic spindle in anaphase: segregation fidelity relies on elaborate mechanics and is dependent on proper chromosome organization. Factors involved in chromosome condensation and genome orgatization are also critical for maintaining genome stability. Together, genome instability and aneuploidy are key factors in malignant progression. Known proteins involved in chromosome architecture are highly conserved between humans and budding yeast (S. cerevisiae). However, many factors involved in these processes remain to be isolated. Since yeasts are genetically tractable, they provide ideal systems in which novel factors required for cellular process can be rapidly identified. Our goal is to identify and understand new budding yeast proteins that control the dynamics of chromosome organization and structure through the cell cycle. Our hypothesis is that human homologs of these proteins will be required to maintain the fidelity of chromosome segregation and the integrity of the genome. These factors will therefore be relevant to the etiology of cancer. Yeast genetic screens will be used to isolate novel mutants defective in chromosome condensation. Two green fluorescent protein (GFP)-tagged chromosome loci, separated by -10-50 kilobases of DNA are visualized as a single discrete fluorescence signal in yeast cells. However, mutants that affect chromosome condensation states will allow the tagged loci to be discerned from one another by fluorescence microscopy. Other phenotypes, such as reduced signal intensity, are also expected in many condensation mutants. Based on these phenotypes, mutants affecting chromosome organization will be identified, both by visual inspection and a combination of automated microscopy and computer-aided diagnosis.