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

• 批准号: 7919426
• 负责人: Amy Joy MacQueen
• 金额: $ 24.65万
• 依托单位: WESLEYAN UNIVERSITY
• 依托单位国家: 美国
• 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/7919426
• 关键词: Address; Alleles; Antibodies; Biochemical; Caenorhabditis elegans; Cell Nucleus; Cells; Centromere; Chromosome Pairing; Chromosome Segregation; Chromosomes; Complex; Defect; Diploidy; Disease; Down Syndrome; Ensure; Event; Exhibits; Failure; Frequencies; Genes; Genetic; Genetic Recombination; Germ Cells; HO nuclease; Hand; Homologous Gene; Human; In Vitro; Infertility; Lead; Learning; Length; Mammals; Measures; Mediating; Meiosis; Meiotic Recombination; Molecular; Molecular Chaperones; Mutation; Organism; Pathway interactions; Peptidylprolyl Isomerase; Phenocopy; Phosphoric Monoester Hydrolases; Play; Positioning Attribute; Post-Translational Protein Processing; Preparation; Process; Prophase; Proteins; Regulation; Reproduction spores; Reproductive Biology; Reproductive Health; Research; Role; Saccharomyces cerevisiae; Saccharomycetales; Screening procedure; Signal Pathway; Site; Structure; Synaptonemal Complex; Transmission Electron Microscopy; Work; Yeasts; gel electrophoresis; homologous recombination; interest; mutant; overexpression; polymerization; prevent; research study

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，染色体开始广泛的重组， 同源染色体，通过联会复合体（SC）沿其长度沿着连接，并且每个都能够 与合作伙伴重组。这一过程对于染色体的精确分离至关重要 在有性生殖生物的配子形成过程中。尽管经过世纪的减数分裂观察 染色体配对和突触在不同的生物体中，基本的分子机制 减数分裂染色体事件仍然是未知的。同源染色体如何相互识别？ 这种初步认识是如何得到加强的？同源物识别是如何与SC组装协调的，使得突触特异性地发生在成对的染色体之间？我已经开始调查这些问题，通过筛选因子，调节SC组装芽殖酵母。我已经确定了至少三种调节突触的分子通路。Fpr3和Rrdl蛋白独立地促进同源物比对缺陷的核中多聚复合物的形成。多复合物是SC组分的焦点积累，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蛋白各自具有脯氨酸异构酶 活性，提高了Zip 1组装SC的能力受伴侣调节的可能性 细胞核中的蛋白质。另一方面，Zip3在阻止SC在染色体上组装中起作用。 当多复合物形成受到损害并且Zip3活性缺失时（如在zip3 fpr3双突变体中），SC组分在染色体上聚集，独立于同源物比对。有趣的是，在zip3 fpr3核中出现的线性SC结构起源于着丝粒区域。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C。线虫配对中心由于Zip3与SC结构组分Zipl在同源物比对之前在着丝粒区域共定位，因此可能Zip3通过调节SC在着丝粒的组装而有助于加强同源物识别。提出的实验使用遗传学、细胞学和生物化学方法来问：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？