Homologous Chromosome Pairing during Meiosis in Yeast

酵母减数分裂过程中的同源染色体配对

• 批准号: 8292984
• 负责人: Sean M Burgess
• 金额: $ 29.29万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8292984
• 关键词: Actins; Affect; Aneuploidy; Biological Assay; Cell Nucleus; Cells; Chromosome Pairing; Chromosome Segregation; Chromosome Structures; Chromosome abnormality; Chromosomes; Congenital Abnormality; DNA; DNA biosynthesis; Data; Defect; Diffusion; Ensure; Event; Fluorescence; Frequencies; Generations; Genes; Genetic; Genetic Crossing Over; Genetic Recombination; Goals; Homologous Gene; Human; Image; Kinetics; Laboratories; Lead; Lesion; Life; Measures; Meiosis; Meiotic Prophase I; Meiotic Recombination; Mental Retardation; Methods; Modeling; Molecular Conformation; Motion; Movement; Mutation; Nuclear Envelope; Nuclear Pore; Outcome; Pathway interactions; Pore Proteins; Process; Role; Spontaneous abortion; Stretching; Structure; Testing; Three-Dimensional Image; Time; Walking; Work; Yeasts; abstracting; base; cancer cell; chromosome movement; fluorophore; genome wide association study; in vivo; mutant; prevent; single molecule; spatial relationship; success; telomere; tool; transmission process

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. PUBLIC HEALTH RELEVANCE: Project Narrative Human reproductive health can be compromised by exposure to myriad compounds found in prescription drugs, food containers and toxic waste products found in the environment. This work is significant because it will identify genetic and biochemical pathways that may be direct targets of these insults during gametogenesis. A detailed understanding of these pathways will aid in identifying the underlying causes of human infertility and birth defects by exposure to environmental contaminants.

描述（由申请人提供）： 项目摘要/摘要由于减数分裂错误导致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递到下一代的保真度。由于缺乏合适的体内工具，对减数分裂配对的彻底机制描述受到阻碍。我们已经开发出允许随着时间的推移快速捕获和分析染色体位点的3D图像的方法。在这里，我们建议使用这些工具来测量同源和异位染色体位点之间的相互作用动力学。然后，我们将探讨配对相互作用如何受到染色体移动和压实等因素的影响。最后，我们将确定限制减数分裂过程中非特异性染色体相互作用的染色体轴的结构特征。我们将首先集中在定义机制，其中Rec8，染色体轴的结构组成部分抑制非特异性染色体减数分裂过程中的相互作用。我们还将进行突变体筛选，以确定其他抑制非特异性配对相互作用的基因。这些研究的结果将有助于了解 减数分裂期间染色体的结构特征与作用于它们的力之间的关系。 公共卫生关系： 人类生殖健康可能会受到暴露于处方药、食品容器和环境中发现的有毒废物中的无数化合物的危害。这项工作是重要的，因为它将确定遗传和生化途径，可能是这些侮辱在配子发生的直接目标。详细了解这些途径将有助于确定人类不育和出生缺陷的根本原因 暴露在环境污染物中。