Chromosome Condensation in Yeast

细胞分裂产生两个新细胞，它只能在细胞内的DNA被复制后发生。这两组相同的重复遗传信息必须被包装成高度紧密的体，称为有丝分裂染色体，以便在两个新细胞之间准确地划分。DNA的这种包装被称为染色体凝聚，如果没有这个过程，有丝分裂的染色体就不能均匀地分布到新细胞中，导致细胞死亡或细胞功能异常。虽然这是一个基本的和必要的生物过程，但执行染色体凝聚的活动尚不清楚。本项目采用新方法，应用于研究染色体凝聚在模式生物，芽殖酵母。出芽酵母的染色体太小，无法看到，因此凝结不能直接检查。为了克服这个问题，该项目使用荧光标记的染色体来可视化活细胞内的凝结。该项目的长期目标是了解染色体凝聚的机制。有两种已知的因素，称为拓扑异构酶II和凝聚蛋白，它们有助于染色体凝聚，但这两种因素都不足以完成这一过程。该项目将确定驱动凝聚的新因素，并将确定拓扑异构酶II和凝聚蛋白是如何调节的，因为这是目前尚不清楚的。该项目的具体目标是：(A)识别和描述新的染色体凝聚因素，(B)确定驱动染色体凝聚的机制，(C)协调多学科研究和培训并传播研究结果。更广泛的影响：酵母作为模型系统的使用很适合本科生、研究生和博士后的教育和培训，因为它允许结合遗传学、细胞生物学和生物化学的多学科研究。此外，酵母方法和酵母遗传筛选特别适合本科研究，因为易于操作和宽容的生长特性。这个项目将涉及一个本科生团队，他们将在酵母遗传学和细胞生物学的许多方面接受培训。一名研究生和一名博士后将在酵母研究方面获得进一步的专业知识，并将获得指导本科生的技能。该项目的科学成果将对科学界产生广泛的影响，超出了确定凝聚机制的主要目标，因为该项目将确定涉及染色体动力学，结构和分离的几个方面的新蛋白质。

Cell division produces two new cells and it can only occur after the DNA in the cell has been duplicated. The two identical duplicate sets of genetic information have to be packaged into highly compact bodies called mitotic chromosomes in order for them to be accurately divided between the two new cells. This packaging of the DNA is termed chromosome condensation and without this process mitotic chromosomes fail to be distributed evenly to the new cells, resulting in cell death or abnormal cell function. Although it is a fundamental and essential biological process, the activities that perform chromosome condensation are not well understood. This project employs new methods applied to the study of chromosome condensation in a model organism, budding yeast. Budding yeast chromosomes are too small to be visualized, thus condensation cannot be examined directly. To overcome this problem, the project uses fluorescent-tagged chromosomes to visualize condensation inside living cells. The long-term goal of the project is to understand the mechanism of chromosome condensation. There are two known factors, called topoisomerase II and condensin, which contribute to chromosome condensation, but neither of these is sufficient for the process. The project will identify new factors that drive condensation and will also determine how topoisomerase II and condensin are regulated as this is not currently understood. The Specific Objectives of the project are to: (A) Identify and characterize novel chromosome condensation factors, (B) Determine the mechanisms that drive chromosome condensation, (C) Orchestrate multi-disciplinary research and training and disseminate the findings.Broader Impact:The use of yeast as a model system lends itself well to the education and training of undergraduate, graduate and post-doctoral students because it allows multi-disciplinary research that combines genetics, cell biology and biochemistry. Moreover, yeast methods and yeast genetic screens in particular are well suited to undergraduate research because of the ease of manipulation and forgiving growth properties. This project will involve a team of undergraduate students who will be trained in many aspects of yeast genetics and cell biology. A graduate student and a post-doctoral student will gain further expertise in yeast research and will gain skills in the mentoring of undergraduate students. The scientific outcomes of the project will have broad impact on the scientific community, beyond the primary goal of identifying the condensation mechanism, because the project will identify new proteins involved in several aspects of chromosome dynamics, structure and segregation.