Meiotic Chromosome Synapsis and Recombination in Yeast

描述（由申请人提供）：我们研究了同源染色体在减数分裂过程中通过重组和重组介导的全染色体配对相互通信的方式。在芽殖酵母中，研究了确保同源染色体之间发生相互作用的过程，而不是有丝分裂重组过程中姐妹篇之间的相互作用，以及通过启动双链断裂（DSB）进行同源性搜索的性质。研究了丝状真菌球孢酵母（Sordaria）的染色体配对.我们的研究将解决的可能性，长距离接触，每染色体配对，干扰/通信之间发展的同源物之间的相互作用和动态运动和重组体介导的影响之间的作用和相互作用在解决染色体纠缠，在配对过程中出现。我们还将确定该生物体中遗传鉴定的DSB/早期重组蛋白的分子性质。我们还研究了如何染色体事件可以发生在一个均匀的间隔模式，没有直接的遗传规格的位置，作为一个模型系统的交叉（CO）重组事件沿沿着减数分裂染色体的图案。我们将通过定量建模进一步研究这一领域的具体问题。我们将继续我们的野生型和突变株芽殖酵母的CO模式的分析和表型和生化分析的特定分子的作用感兴趣。我们还将探讨染色质扩张/收缩状态如何在全球范围内变化，在时间上与减数分裂阶段的相关性，以及在局部，在空间上与CO位点的位置。该分析将包括芽殖酵母中感兴趣的突变体的研究以及Sordaria中新的相关突变体的分离和表征。最后，我们研究重组独立的同源配对，其机制的基础仍然是一个重要的谜的过程。我们将分析我们最近描述的体外DNA/DNA配对过程。同时，我们将进一步研究在芽殖酵母体内配对。我们还将进一步研究丝状真菌脉孢菌似乎涉及直接DNA/DNA配对的现象。 公共卫生相关性：减数分裂是产生用于有性生殖的配子的专门细胞程序。同源染色体之间的相互作用是减数分裂程序的核心，我们的研究解决了这一同源染色体间相互作用程序的三个方面。这个程序中的某些缺陷导致染色体错误分离，这反过来又导致许多重要的遗传疾病。其他缺陷导致无菌。对减数分裂同源物间相互作用的基本理解的进展最终将对诊断和治疗各种生殖缺陷产生影响。

DESCRIPTION (provided by applicant): We investigate the ways in which homologous chromosomes communicate with one another, via recombination and recombination-mediated whole chromosome pairing during meiosis. Recombination is studied in budding yeast with respect to the processes that ensure occurrence of interactions between homologous chromosomes, rather than between sisters as during mitotic recombination, and with respect to the nature of homology searching by an initiating double-strand break (DSB). Recombination- mediated whole chromosome pairing is studied in the filamentous fungus Sordaria. Our studies will address the possibilities of long-range contacts, per-chromosome pairing, interference/communication among developing interhomolog interactions and the roles and interactions among dynamic movement and recombinosome-mediated effects during the resolution of chromosomal entanglements that arise during pairing. We will also determine the molecular natures of genetically-identified DSB/early recombination proteins in this organism. We also investigate how chromosomal events can occur in an evenly-spaced pattern without direct genetic specification of position, using as a model system the patterning of crossover (CO) recombination events along meiotic chromosomes. We will further investigate specific issues in this field by quantitative modeling. We will continue our analysis of CO patterning in wild type and mutant strains of budding yeast and phenotypic and biochemical analysis of the roles of specific molecules of interest. We will also explore how chromatin expansion/contraction status varies globally, in temporal correlation with meiotic stages, and locally, in spatial relation to positions of CO sites. This analysis will include studies of mutants of interest in budding yeast and isolation and characterization of new relevant mutants in Sordaria. Finally, we study recombination-independent homologous pairing, a process whose mechanistic basis remains an important mystery. We will analyze our recently-described in vitro DNA/DNA pairing process. In parallel, we will further examine pairing in vivo in budding yeast. We will also further investigate a phenomenon of filamentous fungus Neurospora that appears to involve direct DNA/DNA pairing. PUBLIC HEALTH RELEVANCE: Meiosis is the specialized cellular program that yields gametes for sexual reproduction. Interactions between homologous chromosomes lie at the heart of the meiotic program and our research addresses three aspects of this inter-homolog interaction program. Certain defects in this program result in chromosome mis-segregation, which, in turn, accounts for many important genetic diseases. Other defects result in sterility. Advances in fundamental understanding of meiotic inter-homolog interactions will ultimately have implications for diagnosis and, hopefully treatment of diverse reproductive defects.