Studies of Synaptonemal Complex in C. elegans Meiosis

癌细胞的一个特征是非整倍体，细胞分裂时染色体再分配的错误是维持正确染色体数目错误的主要原因。减数分裂是一种特殊的细胞分裂形式，染色体数量减少一半，产生单倍体配子。为了避免在细胞分裂过程中染色体的再分配出现错误，利用了一系列的机制来调节染色体分离。突触复合体（SC）是用于这一目的的最重要的结构之一。这种结构“拉链”对同源染色体保持他们稳定地排列在一起。重组是在完全形成的SC的背景下完成的。通过识别SC的组成部分，它们之间如何相互作用，与染色体和重组机制，我们将能够识别导致不分离增加和随之而来的灾难性后果（如流产和出生缺陷）的错误。通过这项研究的目标是：1)通过以下方法检查候选SC成分在SC结构形成中的参与：a-通过荧光原位杂交（FISH）确认这些候选SC成分在突触中的作用；b-在野生型和突触缺陷突变体中进行抗体和GFP融合蛋白的定位；c-通过电子显微镜（EM）分析确定突变体SC形成的程度。2)通过双混合屏幕识别突触所需的新组件。3)研究假定的SC组件之间的物理相互作用。4)评估突触与减数分裂重组的关系。

A hallmark of cancerous cells is aneuploidy and a main source for errors in maintaining correct chromosome number are errors in chromosome redistribution upon cell division. Meiosis is a specialized form of cell division upon which chromosome number is reduced by half generating haploid gametes. In order to avoid errors in the redistribution of chromosomes during cell division, a series of mechanisms are utilized to regulate chromosomal segregation. One of the most important structures employed for this purpose is the synaptonemal complex (SC). This structure "zippers-up" pairs of homologous chromosomes maintaining them stably aligned with each other. Recombination is completed in the context of the fully formed SC. By identifying the components of the SC, how they interact among themselves, with the chromosomes and with the recombination machinery, we will be able to identify the errors that lead to increased nondisjunction and consequent disastrous outcomes such as miscarriages and birth defects. The goals through this fellowship are to: 1) Examine the participation of candidate SC components in the formation of the SC structure by: a- confirming a role in synapsis for these candidates through fluorescence in situ hybridization (FISH); b- performing localization of antibodies and GFP fusion proteins obtained for these candidates, in both, wild type and synapsis defective mutants; c- determining the extent of SC formation in the mutants via electron microscope (EM) analysis. 2) Identify new components required for synapsis by a two-hybrid screen. 3) Investigate the physical interactions among the putative SC components. 4) Assess the relationship between synapsis and meiotic recombination.