Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae

酿酒酵母减数分裂过程中联会复合体组装的调控

基本信息

批准号：
7847932
负责人：
Amy Joy MacQueen
金额：
$ 24.9万
依托单位：
WESLEYAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7847932
关键词：
Alleles Antibodies Behavior Biochemical C-terminal Caenorhabditis elegans Cell Nucleus Cells Centromere Chromosome Pairing Chromosome Segregation Chromosomes Complex Data Defect Detection Diploidy Disease Down Syndrome Electrophoresis Event Exhibits Failure Funding Gel Genes Genetic Genetic Recombination Genetic Screening Germ Cells Goals HO nuclease Hand Homologous Gene Human Infertility Investigation Label Lead Learning Length Mammals Mass Spectrum Analysis Meiosis Meiotic Recombination Modeling Molecular Molecular Chaperones Monitor Mutation Organism Pathway interactions Peptidylprolyl Isomerase Phenocopy Phenotype Play Positioning Attribute Post-Translational Protein Processing Preparation Process Progress Reports Prophase Protein Isoforms Proteins Psychological reinforcement Reading Regulation Reporting Reproductive Health Research Role Saccharomyces cerevisiae Saccharomycetales Screening procedure Signal Transduction Site Structure Synaptonemal Complex Testing Update Yeasts abstracting design gel electrophoresis interest mutant overexpression polymerization prevent recombinational repair research study two-dimensional

项目摘要

At the start of meiosis, chromosomes initiate an extensive reorganization that culminates in aligned homologous chromosomes, joined along their lengths by synaptonemal complex (SC), and each capable of undergoing recombination with its partner. This process is critical for accurate chromosome segregation during gamete formation in sexually reproducing organisms. Despite over a century of observing meiotic chromosome pairing and synapsis in diverse organisms, the molecular mechanisms underlying fundamental meiotic chromosomal events are still unknown. How do homologous chromosomes identify one another? How is this initial recognition reinforced? How is homolog recognition coordinated with SC assembly, such that synapsis occurs specifically between paired chromosomes? I have begun to investigate these questions by screening for factors that regulate SC assembly in budding yeast. I have identified at least three molecular pathways that regulate synapsis. The Fpr3 and Rrdl proteins independently promote the formation of poly complex in nuclei that are defective in homolog alignment. Polycomplexes are focal accumulations of SC components that reflect a failure in SC polymerization on chromosomes, and frequently occur in mutants with early meiotic defects in pairing or recombination. The Fpr3 and Rrdl proteins each have proline isomerase activity, raising the possibility that the capacity of Zip 1 to assemble SC is under regulation by chaperone proteins in the nucleus. Zip3, on the other hand, plays a role in preventing SC assembly on chromosomes. When polycomplex formation is compromised and Zip3 activity is missing, (as in a zip3 fpr3 double mutant), SC components polymerize on chromosomes, independent of homolog alignment. Interestingly, the linear SC structures that arise in zip3 fpr3 nuclei originate from centromere regions. This suggests a role for centromeres in coordinating major meiotic chromosomal events and draws an interesting parallel between yeast centromeres and C. elegans Pairing Centers. As Zip3 colocalizes with the SC structural component, Zipl, at centromere regions prior to homolog alignment, perhaps Zip3 contributes to reinforcing homolog recognition by regulating SC assembly at centromeres. The experiments proposed use genetic, cytological and biochemical approaches to ask: How do Fpr3, Rrdl and Zip3 regulate SC assembly? What is the molecular relationship between SC assembly, recombination and homolog pairing?

在减数分裂开始时，染色体启动广泛的重组，最终形成排列整齐的染色体同源染色体，通过联会复合体（SC）沿其长度连接，并且每条染色体都能够正在与合作伙伴重组。此过程对于准确的染色体分离至关重要在有性生殖生物的配子形成过程中。尽管观察减数分裂已有一个多世纪不同生物体中染色体配对和突触的基本分子机制减数分裂染色体事件仍然未知。同源染色体如何相互识别？这种最初的认知是如何被强化的？同源识别如何与 SC 组装协调，使得突触发生在配对染色体之间？我已经开始通过筛选调节芽殖酵母 SC 组装的因子来研究这些问题。我已经确定了至少三种调节突触的分子途径。 Fpr3 和 Rrdl 蛋白独立地促进同源比对缺陷的核中多聚复合物的形成。多复合物是 SC 成分的集中积累，反映了染色体上 SC 聚合的失败，并且经常发生在配对或重组中具有早期减数分裂缺陷的突变体中。 Fpr3 和 Rrdl 蛋白均具有脯氨酸异构酶活动，增加了 Zip 1 组装 SC 的能力受到伴侣调节的可能性细胞核中的蛋白质。另一方面，Zip3 则在阻止 SC 在染色体上组装方面发挥作用。当多复合物形成受到损害并且 Zip3 活性缺失时（如 zip3 fpr3 双突变体），SC 成分在染色体上聚合，与同源比对无关。有趣的是，zip3 fpr3 核中出现的线性 SC 结构源自着丝粒区域。这表明着丝粒在协调主要减数分裂染色体事件中的作用，并在酵母着丝粒和线虫配对中心之间得出了有趣的相似之处。由于Zip3在同源比对之前与SC结构成分Zip1共定位于着丝粒区域，因此也许Zip3通过调节着丝粒处的SC组装有助于增强同源识别。实验建议使用遗传、细胞学和生化方法来询问：Fpr3、Rrdl 和 Zip3 如何调节 SC 组装？ SC组装、重组和同源配对之间的分子关系是什么？