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(申请人提供)：我们的长期目标是了解基因重组如何有助于染色体的忠实遗传。遗传重组对有性繁殖生物体至关重要，因为同源染色体的DNA分子之间的交叉重组事件以及由此产生的交叉，是减数分裂I分裂中适当的染色体分离所必需的。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体，这是人类流产和出生缺陷的主要原因之一。大多数生物每对染色体很少发生交叉(通常是一两个)，这表明必须严格控制这一过程，以确保每对染色体在每次减数分裂中至少经历一次交叉。尽管最近在了解减数分裂重组的机制及其发生的结构背景方面取得了重大进展，但控制交叉调控的机制仍然知之甚少。我们建议使用线虫来研究减数分裂交叉控制的机制，线虫是一个简单的后生动物实验系统，在这个系统中，已经建立了研究减数分裂的遗传、细胞学和分子工具，并且已经展示了强大的染色体范围内对交叉的调节。我们将通过研究减少已知轴和联会复合体(SC)的功能或丰度的影响来检验这一交叉控制机制需要减数分裂染色体轴或联会复合体(SC)结构完整性的假设。我们将使用遗传和功能基因组学方法来鉴定交叉控制机制的组件，并使用我们开发的一系列分析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蛋白在启动重组以及促进交叉和功能性交叉的调节形成中的作用。最后，我们将调查我们在这项工作中确定的减数分裂重组机制中新组件的作用。