Homologous chromosome pairing during meiosis in yeast

酵母减数分裂过程中的同源染色体配对

基本信息

批准号：
7476512
负责人：
Sean M Burgess
金额：
$ 27.28万
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 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7476512
关键词：
Address Affect Anaphase Aneuploidy Base Pairing Biological Assay Candidate Disease Gene Cells Chromatin Chromatin Structure Chromosome Pairing Chromosome Segregation Chromosome Structures Chromosomes Condition Congenital Abnormality DNA biosynthesis DNA chemical synthesis DNA damage checkpoint Defect Dose Double Strand Break Repair Down Syndrome Embryo Enzymatic Biochemistry Event Frequencies Future Generations Gene Mutation Genes Genetic Recombination Genome Genomics Germ Cells Health Homologous Gene Hot Spot Human Kinetics Lead Link Measures Meiosis Meiotic Prophase I Meiotic Recombination Molecular Genetics Motion Movement Nuclear Envelope Numbers Pathway interactions Pharmaceutical Preparations Phenotype Positioning Attribute Pregnancy loss Process Protein Binding Proteins Relative (related person)Reporting Research Research Personnel Role Saccharomycetales Site Spottings Structure System Telomere Recombination Telomere-Binding Proteins Testing Variant Yeasts cancer cell cell type chromatin immunoprecipitation chromatin remodeling chromosome movement egg homologous recombination mutant programs repaired research study segregation sperm cell telomere tool

项目摘要

DESCRIPTION (provided by applicant): Our objective is to understand how homologous recombination and telomere organization contribute to the juxtaposition of homologous chromosomes in meiosis. These processes are essential to proper chromosome segregation at anaphase I. Defects in these processes can lead to aneuploid gametes, which contribute to birth defects in humans. Mechanisms underlying these processes (double-strand break repair, telomere integrity and chromosome organization) contribute directly to the genesis of cancer cells. How homologs pair is a major unanswered question in the study of meiosis. We propose experiments using budding yeast to address two central questions: i) to what extent do base-pairing interactions contribute to the ability of homologous chromosomes to find one another? And ii) what defines the mechanistic link between dynamic organization of telomeres, recombination, and close, stable homolog juxtaposition (CSHJ). Our hypothesis is that a specific mechanistic step of recombination depends in part on telomere integrity, position or motion. This step is the stabilization of strand-invasion intermediates. A telomere-bound protein, Ndj1, is involved in linking telomere function to chromosome recombination and segregation in meiosis. We propose roles for chromatin structure and DNA damage checkpoint proteins in achieving CSHJ. 1. We will determine the mechanistic step(s) in meiotic recombination that lead to CSHJ. We will use a new quantitative assay that reports on the relative spatial position or accessibility of two chromosomal loci. 2. We will determine the specific features of meiotic telomere reorganization that impact meiotic recombination. We will explore the potential roles of spatial constraint, chromosome motion and a possible direct role in recombination by Ndj1 or other known telomere-bound proteins. 3. We will identify genes by mutation that act in concert with Ndj1 to promote the stabilization of strand invasion intermediates. Genome-wide and candidate gene approaches will be taken. Lay description: Pregnancy loss and birth defects result from embryos having abnormal chromosome numbers (e.g. trisomy 21 or Downs syndrome). This research focuses on understanding how chromosomes are properly distributed to sperm and egg cells. Our findings will impact health of future generations.

描述（由申请人提供）：我们的目标是了解同源重组和端粒组织如何促进减数分裂中同源染色体的并置。这些过程对于正后期的适当染色体分离至关重要。这些过程中的缺陷可能导致非整倍型配子，这会导致人类的出生缺陷。这些过程（双链破裂修复，端粒完整性和染色体组织）背后的机制直接促进了癌细胞的起源。同源物如何在减数分裂研究中是一个主要的未解决问题。我们提出了使用芽酵母解决两个核心问题的实验：i）碱基的相互作用在多大程度上有助于同源染色体互相找到彼此的能力？ ii）什么是定义端粒，重组和近距离稳定同源物并置（CSHJ）的动态组织之间的机械联系。我们的假设是，重组的特定机械步骤部分取决于端粒完整性，位置或运动。此步骤是稳定弹性侵入中间体。端粒结合的蛋白NDJ1参与将端粒功能与减数分裂中的染色体重组和隔离联系起来。我们提出了染色质结构和DNA损伤检查点蛋白在达到CSHJ中的作用。 1。我们将确定导致CSHJ的减数分裂重组的机械步骤。我们将使用一种新的定量测定法，以报告两个染色体基因座的相对空间位置或可及性。 2。我们将确定影响减数分裂重组的减数分裂端粒重组的具体特征。我们将探讨空间约束，染色体运动的潜在作用以及NDJ1或其他已知的端粒结合蛋白重组中可能的直接作用。 3。我们将通过与NDJ1协同作用的突变鉴定基因，以促进链入侵中间体的稳定。将采取全基因组和候选基因方法。外行描述：妊娠丧失和出生缺陷是由于胚胎异常染色体数（例如三体疾病或唐斯综合征）引起的。这项研究的重点是了解如何将染色体正确分配给精子和卵细胞。我们的发现将影响子孙后代的健康。