Meiotic Chromosome Synapsis and Recombination in Yeast

酵母减数分裂染色体联会和重组

• 批准号: 9114150
• 负责人: Nancy E Kleckner
• 金额: $ 85.16万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9114150
• 关键词: Accounting; Address; Affect; Alleles; Arabidopsis; Area; BRCA2 gene; Base Pairing; Biological; Caenorhabditis elegans; Cell Cycle; Cells; Chromatids; Chromatin; Chromosome Pairing; Chromosomes; Collaborations; Communication; Contracts; Cytology; DNA; Defect; Diagnosis; Diffuse; Down Syndrome; Ensure; Event; Evolution; Exhibits; Funding; Gender; Genetic; Genetic Phenomena; Genetic Recombination; Geometry; Germ Cells; Grant; Health; Heart; Hereditary Disease; Homeostasis; Homologous Gene; Human; Image; Imagery; Infertility; Laboratories; Lasers; Length; Life; Mechanical Stress; Mediating; Mediator of activation protein; Meiosis; Meiotic Recombination; Methods; Methyltransferase; Molecular; Motion; Movement; Mutation; Nature; Neurospora crassa; Optic Chiasm; Paris, France; Pathway interactions; Pattern; Peptides; Point Mutation; Polyploidy; Positioning Attribute; Process; Prophase; Protein Analysis; Proteins; Proteomics; RNA; Reproduction; Research; Resolution; Role; Sister; Site; Staging; Sterility; Structure; Synaptonemal Complex; System; Time; Topoisomerase II; Untranslated RNA; Work; Yeasts; base; cohesin; cohesion; comparative; condensin; density; malignant breast neoplasm; mathematical analysis; mutant; nanosurgery; novel strategies; programs; reproductive; research study; segregation; simulation; telomere; tool; transcriptome sequencing

 DESCRIPTION (provided by applicant): We investigate the processes involved in communication along and between homologous chromosomes during meiosis, the specialized cell cycle that underlies gamete formation for sexual reproduction. Importantly, defects in meiosis underlie human infertility and several genetic diseases, notably Downs Syndrome. Proposed research addresses three broad areas. I. We investigate how chromosomal events can occur in an evenly-spaced pattern without direct genetic specification of position. In particular, such patterning is exhibited by meiotic crossovers, manifested originally in the genetic phenomenon of "crossover interference" and subsequently by cytological analyses of crossover-correlated structures along elongated mid-prophase chromosomes and later as points of connections between homologs along partially compacted diplotene chromosomes ("chiasmata"). We are using imaging, proteomics, genetics, mathematical simulations, and laser nanosurgery to address three questions: (A) What molecules are involved in interference? (B) What are the biological implications of this patterning? (C) Does communication occur by redistribution of mechanical stress, as we have proposed? II. We investigate homologous chromosome pairing, a central universal feature of the meiotic program, again by three entry points. (A) We have developed a uniquely powerful system for 3D tracking of homologously-pairing FROS foci in living meiotic yeast cells, with images collected densely over the entire time period of meiosis. This system is poised to address recombination-dependent and -independent pairing and the nature and roles of motion during the pairing period. (B) Meiotic homolog pairing involves both avoidance and active elimination of entanglements (interlocks). By tracking chromosome paths in Sordaria, we can now answer two key questions. (i) What is the mechanism of interlock resolution (by TopoII or by telomere-led movement)? (ii) Does the classical bouquet stage mediate initial homolog contact for pairing or is it involved primarily in ensuring regular topological relationships? (C) Our evidence suggests that repeat-induced point mutation (RIP) in Neurospora crassa involves recombination-independent DNA/DNA pairing. As a second approach to DSB-independent pairing, we are searching for functions required for RIP. III. Meiotic recombination occurs in close physical and functional interaction with chromosome structural axes and, once it forms between axes, the synaptonemal complex (SC). In Sordaria, we will extend recent findings which: (A) begin to elucidate a molecular pathway of events at the critical mid-prophase transition when SC is installed; (B) suggest a new idea for how chromatid axes become "exchanged" at sites of DNA crossovers; and reveal that breast cancer-related BRCA2 has diverse roles for chromosomes beyond those attributable to its canonical role as a Rad51 mediator. Finally, to open an entirely new window onto the meiotic process, we will develop a system for identification and analysis of Sordaria meiotic non-coding RNAs.

 描述（由适用提供）：我们研究减数分裂过程中沿着沿线和同源染色体之间涉及的过程的过程，这是与配子形成有性繁殖的专门细胞周期。重要的是，减数分裂的缺陷是人类不育症和几种遗传疾病的基础，尤其是Downs综合征。拟议的研究涉及三个广泛的领域。 I.我们研究了染色体事件如何以均匀间隔的模式发生，而无需直接的位置遗传规范。特别是，这种模式是由减数分裂跨界暴露的，最初表现在“跨界干扰”的遗传现象，然后通过沿延长的中期中期染色体的交叉相关结构的细胞学分析，后来作为沿着部分压缩的外诺氏素铬烯层沿沿部分压缩的同源物之间的连接点作为chialosomes（chialosomes）（“” Chialsamata。我们使用成像，蛋白质组学，遗传学，数学模拟和激光纳米外科来解决三个问题：（a）哪些分子涉及干扰？ （b）这种图案的生物学意义是什么？ （c）正如我们提出的那样，是否通过机械应力重新分布进行沟通？ ii。我们研究了同源染色体配对，这是减数分裂程序的中枢性特征，再次提出了三个入口点。 （a）我们已经开发了一个具有独特功能的系统，用于在活物质酵母菌细胞中对同源的Fro Foci进行3D跟踪，并且整个时间内都收集了图像 减数分裂时期。该系统被中毒以解决重组依赖性和独立的配对以及配对期间运动的性质和作用。 （b）减数分裂同源配对涉及回避和积极消除纠缠（互锁）。通过跟踪Sordaria的染色体路径，我们现在可以回答两个关键问题。 （i）互锁分辨率的机制是什么（通过topoii或通过端粒领导的运动）？ （ii）经典花束阶段是否介导了配对的初始同源物接触，还是主要涉及确保常规拓扑关系？ （c）我们的证据表明，神经孢子虫中重复诱导的点突变（RIP）涉及与重组无关的DNA/DNA配对。作为独立DSB配对的第二种方法，我们正在寻找RIP所需的功能。 iii。减数分裂重组发生在与染色体结构轴的紧密相互作用和功能性相互作用中，一旦在Sordaria中，我们将扩展最新发现，这些发现：（a）在安装SC时开始阐明临界中期中期过渡过程中事件的分子途径； （b）提出了一个新的想法，即如何在DNA跨界部位“交换”染色单体轴；并揭示了与乳腺癌相关的BRCA2在染色体中具有众多染色体的作用。最后，为了打开一个全新的减数分裂过程，我们将开发一个系统，用于识别和分析Sordaria Meiotic非编码RNA。