ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST

减数分裂是生物有性繁殖的基本过程 为了减少生殖细胞中染色体数目的一半而进行。 这种减少是必要的，这样当两个配子融合在一起时， 受精后，细胞的二倍体染色体数目被重建。 当减数分裂失败，染色体不平衡的配子的结果。在哺乳动物中， 这种染色体不平衡的受精产生的合子 配子通常是不能存活的， 自然流产在产生可存活后代的情况下， 精神和形态缺陷，如21三体 (Down的综合征）。了解减数分裂过程 精确分离同源染色体的工作可能最终 提供监测和防止故障所需的知识， 过程 为了使同源染色体在第一次分离时正确分离， 减数分裂时，它们必须首先通过 形成一种多蛋白质结构，称为联会复合体， （SC）。拟议补助金的重点是确定SC如何 在减数分裂过程中组装，以及它如何发挥作用， 在酵母减数分裂I中同源染色体的两极 酿酒酵母两个基因，RUM 17和RUM 18，最近已经被发现。 使用特异性筛选参与减数分裂的基因来鉴定 染色体联会这些基因中的突变体表现出降低的 同源重组和孢子活力降低。此外，本发明还提供了一种方法， 酰基转移酶HCS 1 -7能够 特异性抑制联会复合体成分中的缺陷 霍皮将接受调查。为了找到其他重要的基因 对于突触，两种遗传筛选，高拷贝抑制和合成 孢子致死率，将使用特别选择的等位基因进行 HOP 1、RED 1、MEK 1和HCS 1 -7。基因突变由遗传 屏幕将分析其对SC形成，重组， 和染色体分离来评估它们的功能。生化 使用纯化的蛋白质和提取物的组合的实验将 以确定是否基因产物， 通过直接的物理相互作用来遗传。特别是 RED 1与HOP 1物理相互作用的模型，以及 HOPI是将测试的MEK 1激酶的底物。通过组合 遗传学、生物化学和细胞学研究， SC的功能、结构和组装途径将被 得到了

Meiosis is a fundamental process that sexually reproducing organisms undergo in order to reduce by half the chromosome number in germ cells. This reduction is necessary so that when two gametes fuse at fertilization the diploid chromosome number of the cell is reconstituted. When meiosis fails, chromosomally imbalanced gametes result. In mammals, the zygotes generated by fertilization of such chromosomally imbalanced gametes are frequently inviable and account for a large number of spontaneous abortions. In cases where viable offspring are produced, mental and morphological defects such as those seen for Trisomy 21 (Down's syndrome) are observed. Understanding how the meiotic process works to accurately segregate homologous chromosomes may ultimately provide the knowledge needed to monitor and prevent failures of the process. In order for homologous chromosomes to segregate properly at the first meiotic division, they must first become physically associated by formation of a multi-protein structure called the synaptonemal complex (SC). The focus of the proposed grant is to determine how the SC is assembled during meiosis and how it functions to direct the segregation of homologous chromosomes to opposite poles at Meiosis I in the yeast Saccharomyces cerevisiae. Two genes, RUM17 and RUM18, have been recently identified using a screen specific for genes involved in meiotic chromosome synapsis. Mutants in these genes exhibit reduced levels of interhomolog recombination and decreased spore viability. In addition, the mechanism by which an acyltransferase, HCS1-7, is able to specifically suppress a defect in the synaptonemal complex component HOPI, will be investigated. In order to find additional genes important for synapsis, two genetic screens, high copy suppression and synthetic spore lethality, will be performed using specially selected alleles of HOP1, RED1, MEK1 and HCS1-7. Mutations in genes arising from the genetic screens will analyzed for their effects on SC formation, recombination and chromosome segregation to assess their functions. Biochemical experiments using a combination of purified proteins and extracts will be performed to determine whether gene products which interact genetically do so by a direct physical interaction. Specifically the model that RED1 physically interacts with HOP1, as well as the model that HOPI is a substrate for the MEK1 kinase will be tested. By combining genetic, biochemical and cytological studies, a greater understanding of the function, structure and pathway of assembly of the SC will be obtained.