Meiotic Chromosome Synapsis and Recombination in Yeast

描述(申请人提供)：我们研究同源染色体在减数分裂过程中通过重组和重组介导的整个染色体配对相互沟通的方式。在萌芽酵母中，重组的研究涉及到确保同源染色体之间发生相互作用的过程，而不是在有丝分裂重组过程中姐妹之间的相互作用，以及通过启动双链断裂(DSB)进行同源搜索的性质。对丝状真菌Sordaria进行了重组介导的全染色体配对研究。我们的研究将讨论远程接触、每条染色体配对、发展中的同源相互作用之间的干扰/通信的可能性，以及动态运动和重组体介导的效应在解决配对过程中出现的染色体纠缠过程中的作用和相互作用。我们还将确定这种生物中遗传识别的DSB/早期重组蛋白的分子性质。我们还研究了染色体事件如何在没有直接遗传位置指定的情况下以均匀分布的模式发生，并使用沿着减数分裂染色体的交叉(CO)重组事件的模式作为模型系统。我们将通过定量建模进一步研究这一领域的具体问题。我们将继续分析萌芽酵母野生型和突变型菌株中的CO模式，并对特定感兴趣分子的作用进行表型和生化分析。我们还将探索染色质扩展/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相关，在局部与CO位置的空间关系中变化。这项分析将包括对发芽酵母感兴趣的突变体的研究，以及分离和鉴定Sordaria中新的相关突变体。最后，我们研究了重组独立的同源配对，这一过程的机制基础仍然是一个重要的谜。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萌芽酵母中的体内配对。我们还将进一步研究丝状真菌Neuropora的现象，该现象似乎涉及直接的DNA/DNA配对。 公共卫生相关性：减数分裂是产生配子进行有性繁殖的专门细胞程序。同源染色体之间的相互作用位于减数分裂计划的核心，我们的研究解决了这种同源染色体间相互作用计划的三个方面。该程序中的某些缺陷会导致染色体错误分离，进而导致许多重要的遗传病。其他缺陷会导致不育。减数分裂同源基因间相互作用的基本了解的进展最终将对各种生殖缺陷的诊断和治疗产生影响。

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.