Homologous Chromosome Pairing during Meiosis in Yeast

描述(由申请人提供)： 项目摘要/摘要减数分裂错误引起的染色体异常是人类出生缺陷和自然流产的主要原因。这项工作的长期目标是阐明减数分裂配对的机制，并了解这些机制如何有助于确保染色体从一代传到下一代的保真度。由于缺乏适当的活体工具，对减数分裂配对的全面机制描述一直受到阻碍。我们开发了一种方法，可以随着时间的推移快速捕获和分析染色体位置的3D图像。在这里，我们建议使用这些工具来测量同源和异位染色体基因座之间的相互作用动力学。然后，我们将探索配对相互作用如何受到染色体移动和紧凑等因素的影响。最后，我们将确定在减数分裂过程中限制非特定染色体相互作用的染色体轴的结构特征。我们将首先专注于确定在减数分裂过程中，染色体轴的结构成分Rec8抑制非特异性染色体相互作用的机制。我们还将进行突变筛选，以确定抑制非特异性配对相互作用的其他基因。这些研究的结果将有助于理解 减数分裂过程中染色体结构特征与作用力之间的关系。

DESCRIPTION (provided by applicant): Project Summary/Abstract Chromosome abnormalities due to meiotic errors are a leading cause of birth defects and spontaneous abortions in humans. The long-term objective of this work is to elucidate the mechanisms of meiotic pairing and to understand how these mechanisms help to ensure the fidelity of chromosome transmission from one generation to the next. A thorough mechanistic description of meiotic pairing has been hindered by the lack of appropriate in vivo tools. We have developed methods that allow the rapid capture and analysis of 3D images of chromosomal loci over time. Here we propose the use of these tools to measure the interaction kinetics between homologous and ectopic chromosomal loci. We will then explore how pairing interactions are affected by factors such as chromosome movement and compaction. Finally, we will identify structural features of the chromosome axis that limit non-specific chromosome interactions during meiosis. We will focus first on defining mechanisms by which Rec8, a structural component of the chromosome axis inhibits nonspecific chromosome interactions during meiosis. We will also carry out a mutant screen to identify other genes that suppress nonspecific pairing interactions. The results of these studies will lead to an understanding of the relationship between the structural features of chromosomes during meiosis and the forces that act upon them.