Synaptonemal complex assembly and function in meiosis

减数分裂中的联会复合体组装和功能

• 批准号: 6970491
• 负责人: Monica P Colaiacovo
• 金额: $ 32.21万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6970491
• 关键词: Caenorhabditis elegans; RNA interference; cell component structure /function; chromosome aberrations; chromosome movement; electron microscopy; fluorescent in situ hybridization; functional /structural genomics; guinea pigs; immunoelectron microscopy; immunoprecipitation; laboratory rabbit; macromolecule; meiosis; molecular assembly /self assembly; nuclear matrix; polymerase chain reaction; regulatory gene; yeast two hybrid system

DESCRIPTION (provided by applicant): Meiosis is a specialized cell division process essential for sexual reproduction that unfolds in two phases (meiosis I and meiosis II) through which chromosome number is reduced by half generating haploid gametes. To segregate properly, chromosomes must undergo a series of steps that are unique to the first meiotic division, including (1) pairing with their homologous partners, (2) formation of a proteinaceous structure known as the synaptonemal complex (SC) along paired and aligned homologous chromosomes, and (3) completion of meiotic recombination leading to physical attachments (chiasmata) between homologs. Significantly, errors in any of these steps lead to chromosome nondisjunction, with disastrous consequences for the embryo. In humans, such events result in miscarriages and birth defects such as Down syndrome. Our focus is on investigating the roles and the macromolecular assembly of the SC, a structure at center stage during meiosis, whose functions are poorly understood and a matter of much debate despite its ubiquitous presence from yeast to mammals. Our studies are performed in the nematode C. elegans, a genetically amenable system in which abundant molecular and biochemical tools can be coupled with powerful cytological approaches. We have recently identified three critical SC components (SYP-1, SYP-2, and SYP-3). Beginning with the analysis of these components, we propose to address fundamental issues concerning the SC, including its assembly and disassembly, composition, and roles in homologous chromosome pairing, meiotic recombination, and chromosome segregation. We will do this by combining our cytological observations done in the context of an intact 3-D nuclear architecture in this system, with results from genetic and biochemical approaches, and a powerful genome-wide functional genomics screen involving RNA-mediated interference.

描述（由申请人提供）：减数分裂是有性繁殖必不可少的专门细胞分裂过程，在两个阶段（减数分裂I和减数分裂II）中展开了必不可少的细胞分裂过程，通过该过程，染色体数量减少了一半产生单倍体配子。为了正确分离，染色体必须经历一系列减数分裂划分的步骤，包括（1）与它们的同源伴侣配对，（2）形成蛋白质结构，称为突触（SC）沿配对和校准的同源铬体和（3）Meiotic Recteragions的chias septry（3）的蛋白质结构（SC）。值得注意的是，这些步骤中的任何一个中的误差会导致染色体非分离，并对胚胎造成灾难性后果。在人类中，这些事件导致流产和唐氏综合症等出生缺陷。我们的重点是研究SC的作用和大分子组装，SC是减数分裂期间中心阶段的结构，尽管酵母到哺乳动物的存在无处不在，但其功能的理解很差，并且存在很多争议。我们的研究是在线虫C.秀丽隐杆线虫中进行的，秀丽隐杆线虫是一种遗传正直的系统，其中大量的分子和生化工具可以与强大的细胞学方法结合在一起。我们最近确定了三个关键SC组件（SYP-1，SYP-2和SYP-3）。从对这些组件的分析开始，我们建议解决有关SC的基本问题，包括其组装和拆卸，组成以及在同源染色体配对，减数分裂重组和染色体隔离中的作用。我们将通过结合在该系统完整的3-D核结构的背景下完成的细胞学观察，以及遗传和生化方法的结果，以及涉及RNA介导的干扰的强大基因组功能基因组学筛查。