Homologous Chromosome Pairing in Meiosis

减数分裂中的同源染色体配对

基本信息

批准号：
9981756
负责人：
Sean M Burgess
金额：
$ 48.28万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9981756
关键词：
3-Dimensional Acute Address Adult Amino Acids Animal Model Architecture Articular Range of Motion Biochemical Pathway Biological Models Cell Nucleus Chromosome Pairing Chromosome Segregation Chromosome Structures Chromosome abnormality Chromosomes Congenital Abnormality Crowding Cytoplasm DNA Double Strand Break DNA Sequence DNA-Protein Interaction Data Drug Prescriptions Elements Embryo Ensure Environment Environmental Hazards Environmental Pollution Event Exposure to Food Container Gametogenesis Generations Genes Genetic Genetic Models Genetic Recombination Genetic Structures Genome Genome engineering Germ Cells Hereditary Disease Homologous Gene Human Image Infertility Kinetics Lead Life Link Liquid substance Measures Meiosis Meiotic Prophase I Mitotic Mitotic Chromosome Modeling Motion Movement Mus Nature Nuclear Nuclear Envelope Nuclear Pore Complex Proteins Nuclear Structure Oogenesis Organism Pathway interactions Play Process Property Prophase Regulation Reproductive Health Research Role SPO11 gene Saccharomycetales Sex Differences Spermatogenesis Spontaneous abortion Structure Technology Time Waste Products Work Yeasts Zebrafish base chromosome movement cost experimental study human disease human male human model in silico insight live cell imaging programs segregation sex telomere tool transmission process

项目摘要

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. While the events of meiosis are well conserved across species, their execution accommodates nuclear volumes and genome sizes that vary by several orders of magnitude. Our aims address the hypothesis that the 3D configurations of chromosomes are discrete, dynamic, and governed in space and time to accommodate the changing nuclear structure/function requirements throughout the course of meiotic prophase. This proposal builds on our recent discovery that a 125 amino acid region of the yeast nucleoporin Nup2 is required for proper chromosome segregation in meiosis, independent of its role in transport. We will determine how this meiotic autonomous region (MAR) functions in carrying out this role using a variety of genetic and structure-based approaches. We also introduce zebrafish as a new genetic model organism to study meiotic chromosome dynamics during oogenesis and spermatogenesis. Our finding so far suggest that zebrafish may an excellent model for human male meiosis. Adult zebrafish produce gametes throughout life, progeny number in the hundreds and embryos develop outside the body. We will determine the spatial and temporal program of homolog pairing, DNA double-strand break formation and synapsis as it relates to the canonical meiosis program in other species. Finally, we will apply a three-dimensional live-cell imaging pipeline we created for budding yeast to measure interaction kinetics between homologous and ectopic chromosomal loci in the two zebrafish sexes. Our results will lead to an understanding of how environmental hazards increase the occurrence of chromosome-based birth defects and inherited disease.

项目概要/摘要减数分裂错误导致的染色体异常是出生缺陷和自发性缺陷的主要原因人类堕胎。这项工作的长期目标是阐明减数分裂配对和减数分裂的机制了解这些机制如何帮助确保染色体传递的保真度一代又一代。虽然减数分裂事件在物种之间得到了很好的保守，但它们的执行容纳变化几个数量级的核体积和基因组大小。我们的目标解决了这样的假设：染色体的 3D 构型是离散的、动态的并且受控于空间和时间以适应整个过程中不断变化的核结构/功能要求减数分裂前期。该提议建立在我们最近的发现之上，即酵母的 125 个氨基酸区域核孔蛋白 Nup2 是减数分裂中正确染色体分离所必需的，与其在减数分裂中的作用无关运输。我们将确定减数分裂自治区 (MAR) 在发挥这一作用时如何发挥作用各种基于遗传和结构的方法。我们还引入斑马鱼作为新的遗传模型有机体研究卵子发生和精子发生过程中的减数分裂染色体动力学。到目前为止我们的发现表明斑马鱼可能是人类雄性减数分裂的绝佳模型。成年斑马鱼产生配子在整个生命过程中，后代数量达到数百个，胚胎在体外发育。我们将确定同源配对、DNA 双链断裂形成和突触的空间和时间程序与其他物种的典型减数分裂程序有关。最后，我们将应用三维活细胞我们为芽殖酵母创建的成像管道，用于测量同源酵母和酵母之间的相互作用动力学两种斑马鱼性别的异位染色体位点。我们的结果将让我们了解如何环境危害增加了染色体出生缺陷和遗传性疾病的发生。