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）： 由于减数分裂错误导致的项目摘要/抽象染色体异常是人类出生缺陷和自发堕胎的主要原因。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从一代到另一代染色体传播的保真度。缺乏合适的体内工具，阻碍了对减数分裂配对的彻底机械描述。我们开发了可以随着时间的推移对染色体基因座的3D图像进行快速捕获和分析的方法。在这里，我们建议使用这些工具来测量同源和异位染色体基因座之间的相互作用动力学。然后，我们将探讨如何受染色体运动和压实等因素影响配对相互作用。最后，我们将确定染色体轴的结构特征，这些特征限制了减数分裂过程中非特异性染色体相互作用。我们将首先关注定义机制，REC8（染色体轴的结构成分）抑制减数分裂过程中非特异性染色体相互作用。我们还将执行一个突变屏幕，以识别抑制非特异性配对相互作用的其他基因。这些研究的结果将导致对 减数分裂过程中染色体的结构特征与作用于它们的力之间的关系。 公共卫生相关性： 通过在环境中发现的处方药，食物容器和有毒废物产品中发现的无数化合物，可以损害人类生殖健康的项目叙事。这项工作很重要，因为它将识别遗传和生化途径，这些途径可能是配子发生过程中这些侮辱的直接靶标。对这些途径的详细理解将有助于确定人类不孕症和先天缺陷的根本原因 通过暴露于环境污染物。