Structure and Dynamics of the Synaptonemal Complex

描述（由申请人提供）： 在减数分裂前期，配偶染色体之间的同源性识别与蛋白质支架的组装相协调，联会复合体（SC），沿着染色体对的长度（联会）。同源物间重组在组装的SC的背景下进行，并且许多同源物间重组事件依赖于SC来进行它们的适当分布和/或完成。我们的实验室研究SC结构和SC组装是如何与减数分裂前期染色体事件协调的。最近，我们证明了在S。在酿酒酵母中，SC的至少一些组分在减数分裂前期保持动态，甚至在染色体完全突触之后。此外，我们发现，重组位点保持不同的SC动态相比，其他网站上的SC。此外，我们的初步研究表明，SUMO，定位于SC结构，有一个相互依赖的关系与卷曲螺旋Zip 1蛋白组装SC减数分裂染色体。通过使用超分辨率光学显微镜的开创性成像研究，我们还表明SUMO定位于SC结构中心的Zip 1 N末端。最后，该实验室已经分离出zip 1等位基因，它们在染色体上的组装不依赖于典型的调节因子。每个zip 1等位基因代表一个单一的氨基酸取代在极端的Zip 1的C末端，并可能揭示Zip 1大会的机制方面。这项资助提案的目的是1）使用我们建立的遗传和显微镜工具来定义SC内所有已知突触蛋白的分子结构和动力学，2）分离突触起始蛋白和Zip 1的点突变等位基因，以确定负责突触和其他减数分裂前期染色体事件中功能的每种蛋白的分子特征。

DESCRIPTION (provided by applicant): Project Summary/Abstract During meiotic prophase, homology recognition between partner chromosomes is coordinated with the assembly of a proteinaceous scaffold, the synaptonemal complex (SC), along the length of the chromosome pair (synapsis). Interhomolog recombination progresses within the context of assembled SC, and many interhomolog recombination events rely on SC for their proper distribution and/or completion. Our lab investigates SC structure and how SC assembly is coordinated with meiotic prophase chromosomal events. Recently we demonstrated that In S. cerevisiae, at least some components of the SC remain dynamic during meiotic prophase, even after chromosomes are fully synapsed. Moreover we found that recombination sites maintain a different SC dynamic as compared to other sites on the SC. Furthermore, our preliminary studies show that SUMO, which localizes to SC structures, has a mutually dependent relationship with the coiled-coil Zip1 protein to assemble SC on meiotic chromosomes. With pioneering imaging studies using super-resolution light microscopy, we have also shown that SUMO localizes to Zip1 N termini, at the center of SC structure. Finally, the lab has isolated zip1 alleles that assemble on chromosomes independent of canonical regulators. Each zip1 allele represents a single amino acid substitution at the extreme C terminus of Zip1 and may reveal aspects of the mechanism underlying Zip1 assembly. The purpose of this grant proposal is to 1) use our established genetic and microscopy tools to define the molecular architecture and dynamics of all known synapsis proteins within the SC, and 2) to isolate point mutant alleles of synapsis initiation proteins and Zip1 in order to identif molecular features of each protein responsible for their function in synapsis and other meiotic prophase chromosomal events.