Genetic and molecular dissection of meiotic silencing and unpaired DNA detection.

描述（由申请人提供）：减数分裂沉默是在动物和真菌中观察到的一种现象，在减数分裂期间，未配对的基因或其他遗传元件被关闭。事实上，它是由未配对的DNA触发的，这使得它非常适合于控制自私的遗传元素，如病毒和转座子。尽管减数分裂沉默似乎是RNA沉默的一种类型——一个泛指真核生物中小RNA介导过程的通称——但对其机制性质知之甚少。本提案的主要目标是研究减数分裂沉默的未知方面，特别是利用最初发现的真核生物：粗神经孢子虫（Neurospora crassa）的未配对DMA检测过程。实现这一目标的具体目标包括：1)开发和实施一种高通量筛选方法来鉴定减数分裂沉默突变体；2)鉴定和表征理论上从未配对的减数分裂DNA转录而来的异常RNA转录物；3)克隆和表征对减数分裂沉默抑制驱动元件具有抗性的等位基因。相关性：人类自私的遗传因素与几种遗传疾病有关。本文提出的研究旨在阐明减数分裂沉默的机制，减数分裂沉默是一个最近发现的生物学过程，可能有助于保护人类基因组免受自私遗传因素的侵害。从这项研究中获得的知识可能有利于未来预防遗传疾病的努力。

DESCRIPTION (provided by applicant): Meiotic silencing is a phenomenon observed in animals and fungi whereby unpaired genes or other genetic elements are turned off during meiosis. The fact that it is triggered by unpaired DNA makes it ideally suited for the control of selfish genetic elements, such as viruses and transposons. Although meiotic silencing appears to be a type of RNA silencing - a generic term referring to small RNA mediated processes in eukaryotes - little else is known about its mechanistic nature. This proposal's primary goal is to investigate the unknown aspects of meiotic silencing, particularly the unpaired DMA detection process, using the eukaryotic organism in which it was initially discovered: Neurospora crassa. Specific aims to reach this goal include: 1) to develop and implement a high-throughput screen to identify meiotic silencing mutants 2) to identify and characterize the aberrant RNA transcripts theorized to be transcribed from unpaired meiotic DNA and 3) to clone and characterize alleles conferring resistance to [meiotic silencing-suppressing] meiotic drive elements. Relevance: Human selfish genetic elements have been linked to several genetic diseases. The research proposed herein seeks to elucidate the mechanism of meiotic silencing, a recently discovered biological process that may help defend the human genome from selfish genetic elements. Knowledge gained from this study could benefit future efforts towards the prevention of genetic disorders.