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：
7893820
负责人：
Sean M Burgess
金额：
$ 26.02万
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/7893820
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 Congenital Abnormality DNA biosynthesis DNA damage checkpoint Defect Dose Double Strand Break Repair Down Syndrome Embryo Enzymatic Biochemistry Event Frequencies Future Generations Gene Mutation Genes Genetic Recombination 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 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 genome-wide 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。这些过程对于后期 I 的正确染色体分离至关重要。这些过程的缺陷可能导致非整倍体配子，从而导致人类出生缺陷。这些过程的潜在机制（双链断裂修复、端粒完整性和染色体组织）直接促成癌细胞的发生。同源物如何配对是减数分裂研究中一个尚未解答的主要问题。我们建议使用芽殖酵母进行实验来解决两个核心问题：i）碱基配对相互作用在多大程度上有助于同源染色体找到彼此的能力？ ii) 端粒的动态组织、重组和紧密、稳定的同源并置 (CSHJ) 之间的机制联系是什么定义的。我们的假设是，重组的具体机制步骤部分取决于端粒完整性、位置或运动。此步骤是链侵入中间体的稳定化。端粒结合蛋白 Ndj1 参与将端粒功能与减数分裂中的染色体重组和分离联系起来。我们提出染色质结构和 DNA 损伤检查点蛋白在实现 CSHJ 中的作用。 1. 我们将确定减数分裂重组中导致 CSHJ 的机制步骤。我们将使用一种新的定量测定来报告两个染色体位点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。我们将探索空间约束、染色体运动的潜在作用以及 Ndj1 或其他已知端粒结合蛋白在重组中可能的直接作用。 3.我们将通过突变鉴定与Ndj1协同作用的基因，以促进链侵入中间体的稳定。将采用全基因组和候选基因方法。外行描述：流产和出生缺陷是由染色体数目异常（例如 21 三体或唐氏综合症）的胚胎引起的。这项研究的重点是了解染色体如何正确分配给精子和卵细胞。我们的研究结果将影响子孙后代的健康。