Genetic and Molecular Study of Meiotic Trans-sensing and Meiotic Silencing

减数分裂转感和减数分裂沉默的遗传和分子研究

• 批准号: 7163542
• 负责人: Rodolfo Aramayo
• 金额: $ 27.6万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163542
• 关键词: Genetic; Molecular; Study; Meiotic; Trans

Homology-sensing mechanisms are critical to meiosis. How homology-sensing is used by chromosomes to find their pairing partners is still a mystery. Yet, genome integrity and the faithful transmission of the genetic information contained in chromosomes depend on these mechanisms. Chromosome pairing is an important and conserved mechanical event. Our working hypothesis is that this mechanical pairing is, in addition, an active "sensing" mechanism used by all meiotic chromosomes to examine their homologues from stem to stern in each meiosis. In this process, chromosomes use the sophisticated meiotic trans-sensing machinery to evaluate their pairing partners. Failure of "sensing" or "pairing" of a discrete DNA region because of the presence of a heterologous region, or the presence of a deletion on the opposite chromosome (i.e., the lack of a homologous region), triggers meiotic silencing-a novel meiotic RNA silencing mechanism. Once activated, the meiotic silencing machinery produces a diffusible silencing signal specific to the unpaired DNA. This signal then, silences the expression of all genes homologous to the ones contained in the unpaired region, whether they are paired or unpaired. The objective of this research is to identify all the players that participate in, and to dissect the molecular mechanisms used by meiotic trans-sensing and meiotic silencing in Neurospora. During this funding period we will develop a series of interrelated projects aimed at defining how homologs "sense" each other and at characterizing mutants affected in these processes. Understanding chromosome sensing is important, for it will lead us to a better understanding of the surveillance mechanisms used by cells to detect "foreign" sequences and how these surveillance mechanisms work to inactivate them, knowledge that has great potential for the therapeutic manipulation of gene expression in all organisms. Understanding these mechanisms can aid our understanding of similar mechanisms in humans, where they participate in both development and disease.

同源传感机制对于减数分裂至关重要。染色体如何利用同源感应来寻找配对伙伴仍然是一个谜。然而，基因组完整性和染色体中所含遗传信息的忠实传递取决于这些机制。染色体配对是一个重要且保守的机械事件。我们的工作假设是，这种机械配对是所有减数分裂染色体使用的一种主动“传感”机制，用于在每次减数分裂中检查其从茎到尾的同源物。在此过程中，染色体使用复杂的减数分裂转感机制来评估其配对伙伴。由于以下原因导致离散 DNA 区域“感知”或“配对”失败 异源区域的存在，或对侧染色体上缺失的存在（即缺乏同源区域），会触发减数分裂沉默——一种新的减数分裂RNA沉默机制。一旦被激活，减数分裂沉默机制就会产生针对未配对 DNA 的可扩散沉默信号。然后，该信号使与未配对区域中包含的基因同源的所有基因的表达沉默，无论它们是配对还是未配对。本研究的目的是确定参与脉孢菌减数分裂转感和减数分裂沉默的所有参与者，并剖析其分子机制。在此资助期间，我们将开发一系列相互关联的项目，旨在定义同源物如何相互“感知”，并表征在这些过程中受影响的突变体。了解染色体传感很重要，因为它将让我们更好地了解 细胞用来检测“外来”序列的监视机制以及这些监视机制如何使它们失活，这些知识对于所有生物体中基因表达的治疗操作具有巨大潜力。了解这些机制可以帮助我们了解人类参与发育和疾病的类似机制。