A Molecular Genetic Analysis of Meiotic Chromosome Nondisjunction

减数分裂染色体不分离的分子遗传学分析

• 批准号: 9507089
• 负责人: Michael Dresser
• 金额: $ 32.63万
• 依托单位: Oklahoma Medical Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9507089&HistoricalAwards=false
• 关键词: Molecular; Genetic; Analysis; Meiotic; Chromosome

9507089 Dresser The long-range goal of this work is to understand how meiosis-specific structures, such as synaptonemal complexes and recombination nodules, are organized and function in meiotic chromosome repair, recombination and segregation. It has been shown that alterations in the stoichiometry of subunits in multicomponent structures can perturb the function of those structures. As a novel first step toward identifying the components of the meiosis-specific structures in the yeast Saccharomyces cerevisiae, cells have been challenged with wild-type yeast DNA carried on plasmids that replicate to 100 or more copies per cell. A sensitive assay for meiotic chromosome nondisjunction has made it possible to identify plasmids carrying inserts that specifically cause errors in meiotic chromosome segregation or prevent the completion of meiosis. Forty-one such plasmids carrying different inserts have been found. Preliminary results indicate that some of the plasmids contain meiotic genes previously identified from recessive mutant hunts; other plasmids contain novel genes, some of which are likely to have been missed in previous searches due to functional overlaps with other genes. Identification of genes in the latter class is particularly timely given the impending completion of the yeast genome sequence, which will greatly facilitate analysis of the functions of families of genes. The work proposed here is (1) to conduct secondary screens on the plasmid collection to identify genes most likely to be directly involved in meiotic chromosome segregation, and (2) to perform immunocytological studies on a subset to identify gene products that are components of meiotic chromosome structures. %%% By identifying and analyzing novel genes and functions required for chromosome repair, recombination and segregation in meiosis, these studies in the yeast model system will contribute to an understanding of how cells in eukaryotes, including humans, keep their genomes intact during this critica l period in the reproductive cycle of sexual organisms. Errors in meiosis can result in cells of the next generation having an abnormal number of chromosomes or in cell death. ***

9507089梳妆台 这项工作的长期目标是了解减数分裂特异性结构，如联会复合体和重组结节，是如何组织和功能的减数分裂染色体修复，重组和分离。 它已被证明，在多组分结构中的亚基的化学计量的改变可以扰乱这些结构的功能。作为鉴定酵母酿酒酵母中减数分裂特异性结构组分的新的第一步，细胞已经用携带在质粒上的野生型酵母DNA进行了挑战，所述质粒复制到每个细胞100个或更多个拷贝。一个敏感的减数分裂染色体不分离的检测方法，有可能确定质粒携带的插入，特别是导致错误的减数分裂染色体分离或阻止减数分裂的完成。 已经发现了41个携带不同插入片段的质粒，初步结果表明，其中一些质粒含有以前从隐性突变体狩猎中鉴定出的减数分裂基因;其他质粒含有新基因，其中一些可能由于与其他基因的功能重叠而在以前的搜索中被遗漏。鉴于酵母基因组序列即将完成，后一类基因的鉴定特别及时，这将极大地促进基因家族功能的分析。 本文提出的工作是（1）对质粒收集物进行二次筛选，以鉴定最有可能直接参与减数分裂染色体分离的基因，以及（2）对一个子集进行免疫细胞学研究，以鉴定作为减数分裂染色体结构组分的基因产物。 通过鉴定和分析减数分裂中染色体修复、重组和分离所需的新基因和功能，这些在酵母模型系统中的研究将有助于理解真核生物（包括人类）中的细胞如何在有性生物生殖周期的关键时期保持其基因组完整。 减数分裂中的错误可导致下一代细胞具有异常数目的染色体或细胞死亡。 ***