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.

项目摘要/摘要由于减数分裂错误导致的染色体异常是出生缺陷和自发的主要原因人类流产。这项工作的长期目标是阐明减数分裂配对的机制和了解这些机制如何有助于确保染色体传播的保真度生成下一个。虽然减数分裂的事件在各种物种之间都得到了很好的保存，但它们的执行可容纳核量和基因组大小，这些大小因几个数量级而异。我们的目标解决以下假设：染色体的3D构型是离散的，动态的，并且在在整个课程中适应不断变化的核结构/功能要求的空间和时间减数分裂的预言。这项提案是基于我们最近发现的，即酵母的125个氨基酸区域核孔蛋白NUP2是减数分裂中适当的染色体隔离所必需的，与其在其中的作用无关运输。我们将确定这个减数分裂自治区域（MAR）在使用此角色中的作用各种基于遗传和结构的方法。我们还引入斑马鱼作为一种新的遗传模型在卵子发生和精子发生过程中研究减少染色体动力学的生物体。到目前为止我们的发现暗示斑马鱼可能是人类减数分裂的绝佳模型。成人斑马鱼农产配子在整个生命中，数百人的后代数量和胚胎在体外发展。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规范减数分裂计划有关。最后，我们将应用三维的活细胞成像管道我们为萌芽的酵母创建了，以测量同源和同源之间的相互作用动力学两种斑马鱼的异位染色体基因座。我们的结果将导致对如何理解环境危害增加了基于染色体的先天缺陷和遗传疾病的发生。