Condensin-mediated Chromosome Organization and Genome Integrity during Meiosis

减数分裂过程中凝缩蛋白介导的染色体组织和基因组完整性

• 批准号: 0718384
• 负责人: Hong-Guo Yu
• 金额: $ 45万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2012-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0718384&HistoricalAwards=false
• 关键词: Condensin; mediated; Chromosome; Organization; Genome

The long-term goal of this project is to elucidate the molecular mechanism responsiblefor the formation of the meiotic chromosome architecture and to examine the role chromosome organization plays in safeguarding genomic integrity. Mitosis and meiosis both require higher-order chromosome organization, which is achieved by the action of a conserved and essential protein complex called condensin. In mitosis, however, there is only one genetic division, that in which paired sister chromatids separate. In contrast, in meiosis two divisions occur. In the first, homologous chromosomes pair, recombine, and then separate; only in the second do the sister chromatids separate. Genetic studies of baker's yeast (Saccharomyces cerevisiae) have confirmed that condensin plays a role in condensation and segregation of meiotic chromosomes. The proposed research is focused on the in vivo cellular and biochemical activities of condensin in meiosis. Three complementary approaches will be employed: (1) A novel three-dimensional chromosome-tracking system will be developed for study of condensin function in chromosome organization and rearrangement at the point of their occurrence in live cells. (2) Genomic and proteomic techniques will be used to identify factors that interact with condensin. Their interaction with condensin will be characterized in the context of DNA topological changes and chromosome segregation. (3) An inducible DNA double-strand break will be created on the chromosome during meiosis so that the role of condensin in repair of the break can be examined. This project involves both undergraduate and graduate students at Florida State University. The feasibility of projects using yeast genetics makes them particularly appropriate and attractive to undergraduate students, including minority students, who participate in a faculty-directed independent study program. This project will therefore enhance the education of undergraduate and graduate students as well as contribute to the advancement of chromosome research.

该项目的长期目标是阐明减数分裂染色体结构形成的分子机制，并研究染色体组织在保护基因组完整性方面所起的作用。有丝分裂和减数分裂都需要高阶染色体组织，这是通过一种称为凝聚蛋白的保守和必需的蛋白质复合物的作用来实现的。然而，在有丝分裂中，只有一种遗传分裂，即成对的姐妹染色单体分离。相反，减数分裂发生两次分裂。首先，同源染色体配对，重组，然后分离；只有在第二种染色单体中姐妹染色单体才会分离。baker's yeast （Saccharomyces cerevisiae）的遗传学研究证实，凝聚蛋白在减数分裂染色体的凝聚和分离中起作用。本文主要研究凝缩蛋白在减数分裂过程中的细胞生化活性。将采用三种互补的方法：(1)开发一种新的三维染色体跟踪系统，用于研究凝缩蛋白在活细胞中染色体组织和重排中的功能。(2)基因组学和蛋白质组学技术将用于识别与凝缩蛋白相互作用的因子。它们与凝缩蛋白的相互作用将在DNA拓扑变化和染色体分离的背景下进行表征。(3)在减数分裂过程中，染色体上会产生可诱导的DNA双链断裂，因此可以研究凝缩蛋白在修复断裂中的作用。这个项目涉及佛罗里达州立大学的本科生和研究生。酵母遗传学项目的可行性使它们特别适合和吸引本科生，包括少数民族学生，他们参加教师指导的独立学习计划。因此，这个项目将加强对本科生和研究生的教育，并促进染色体研究的发展。