Genetic Recombination in C elegans

线虫的基因重组

• 批准号: 6751214
• 负责人: ANNE M VILLENEUVE
• 金额: $ 29.47万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6751214
• 关键词: Caenorhabditis elegans; chromosome movement; chromosomes; cytogenetics; developmental genetics; fluorescent in situ hybridization; functional /structural genomics; genetic crossing over; genetic markers; genetic recombination; genetic screening; green fluorescent proteins; helminth genetics; laboratory rabbit; laboratory rat; meiosis; polymerase chain reaction; single nucleotide polymorphism

DESCRIPTION (provided by applicant): Our long-term goal is to understand how genetic recombination contributes to the faithful inheritance of chromosomes. Genetic recombination is of central importance to sexually reproducing organisms, since crossover recombination events between the DNA molecules of homologous chromosomes, and the resulting chiasmata, are necessary for proper chromosome segregation at the meiosis I division. Failure to form crossovers leads to chromosome missegregation and consequent aneuploidy, one of the leading causes of miscarriages and birth defects in humans. Most organisms make very few crossovers per chromosome pair (often one or two), indicating that the process must be tightly regulated to ensure that each pair will undergo at least one crossover per meiosis. Despite significant recent advances in understanding the mechanisms of meiotic recombination and the structural context in which it occurs, the mechanisms governing crossover regulation remain poorly understood. We propose to investigate the mechanisms of meiotic crossover control using the nematode C. elegans, a simple metazoan experimental system in which genetic, cytological and molecular tools for investigating meiosis are well established, and in which robust chromosome-wide regulation of crossing over has been demonstrated. We will test the hypothesis that structural integrity of the meiotic chromosome axes or the synaptonemal complex (SC) is required for this crossover control mechanism by investigating the effects of reducing function or abundance of known axis and SC components. We will use genetic and functional genomics approaches to identify components of the crossover control machinery, and use a battery of assays we developed to investigate how impairment of these components affects the organization and morphogenesis of meiotic chromosomes and the progress of meiotic recombination. We will investigate the role of the HIM-17 protein the initiation of recombination and in promoting the regulated formation of crossovers and functional chiasmata. Finally, we will investigate the roles of new components of the meiotic recombination machinery that we identify through the course of this work.

描述（由申请人提供）：我们的长期目标是了解基因重组如何促进染色体的忠实遗传。遗传重组对于有性生殖生物体至关重要，因为同源染色体 DNA 分子之间的交叉重组事件以及由此产生的交叉，对于减数分裂 I 分裂中正确的染色体分离是必要的。未能形成交叉会导致染色体错误分离和随之而来的非整倍性，这是人类流产和出生缺陷的主要原因之一。大多数生物体每对染色体进行的交换很少（通常是一到两次），这表明必须严格调控该过程，以确保每对染色体在每次减数分裂时至少经历一次交换。尽管最近在理解减数分裂重组机制及其发生的结构背景方面取得了重大进展，但对交叉调控的机制仍然知之甚少。我们建议使用线虫秀丽隐杆线虫来研究减数分裂交叉控制的机制，这是一个简单的后生动物实验系统，其中已经很好地建立了用于研究减数分裂的遗传、细胞学和分子工具，并且已经建立了强大的全染色体交叉调节。证明了。我们将通过研究减数分裂染色体轴或联会复合体（SC）的结构完整性是这种交叉控制机制所必需的假设，通过研究减少已知轴和 SC 成分的功能或丰度的影响。我们将使用遗传和功能基因组学方法来识别交叉控制机制的组件，并使用我们开发的一系列检测方法来研究这些组件的损伤如何影响减数分裂染色体的组织和形态发生以及减数分裂重组的进展。我们将研究 HIM-17 蛋白在重组启动以及促进交叉和功能交叉的调节形成中的作用。最后，我们将研究我们在这项工作过程中确定的减数分裂重组机制新组件的作用。