Condensin-mediated Chromosome Organization and Genome Integrity during Meiosis

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维护基因组完整性方面的作用。有丝分裂和减数分裂都需要更高级的染色体组织，这是通过一种保守的和必需的蛋白质复合物（称为凝聚素）的作用来实现的。 然而，在有丝分裂中，只有一次遗传分裂，即成对的姐妹染色单体分开。相反，在减数分裂中发生两次分裂。在第一种情况下，同源染色体配对、重组，然后分离;只有在第二种情况下，姐妹染色单体才分离。 对面包酵母（Saccharomycescerevisiae）的遗传学研究已经证实，凝聚素在减数分裂染色体的凝聚和分离中起作用。 本论文主要研究凝聚素在减数分裂过程中的体内细胞和生化活性。三个互补的方法将被采用：（1）一个新的三维染色体跟踪系统将被开发用于研究凝聚素在染色体组织和重排中的功能，在它们发生在活细胞中。 (2)基因组学和蛋白质组学技术将被用来识别与凝聚素相互作用的因子。 它们与凝聚素的相互作用将在DNA拓扑结构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，染色体上会产生一个可诱导的DNA双链断裂，这样就可以检查凝聚素在修复断裂中的作用。 该项目涉及佛罗里达州立大学的本科生和研究生。 使用酵母遗传学的项目的可行性使他们特别适合和吸引本科生，包括少数民族学生，谁参加教师指导的独立研究计划。因此，该项目将加强本科生和研究生的教育，并有助于染色体研究的进步。

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.