ORGANIZATION, EXPRESSION, AND INHERITANCE OF YEAST MTDNA

描述（改编自申请人的摘要）： 建议的研究是了解遗传的机制， 线粒体DNA（mtDNA）的方法。酿酒酵母，作为一个模型， 有机体拟议中的研究将结合联合收割机的遗传，生物化学，分子， 和细胞生物学方法来识别和表征各种 这些成分有助于线粒体DNA的忠实传递， 营养生长为此，研究人员提出了三个具体目标：1） 完成线粒体DNA蛋白的详细生化表征 复合物（类核）是线粒体DNA的分离单位。目标是 通过交联程序鉴定与mtDNA相互作用的主要蛋白质 并确定这些蛋白质如何对组织做出贡献， 线粒体基因组的繁殖。2)分析小说的功能 线粒体DNA交换所需的蛋白质和途径。比如说 研究人员将扩大研究结果，即线粒体：伴侣， Hsp60和一些线粒体蛋白，其表达在一般氨基酸水平下， 酸控制，他们已经发现与线粒体DNA，影响 mtDNA遗传3)分析顺式和反式作用元件控制 线粒体DNA复制和传输在娇小和野生型菌株。这些 研究将集中在假定的复制起点（ori）的作用上。 在过度压抑现象中，ori元素的作用 在野生型mtDNA的复制和传递中的作用， 从ori元素启动滚动复制的活动。如何 细胞传递其mtDNA是基本的，适用于几乎所有真核生物 细胞现在很清楚，一些遗传性疾病涉及以下方面： 突变型和野生型mtDNA的分离。调查人员已 开发了一个易于处理的实验系统来研究这些 重要问题。

DESCRIPTION (adapted from applicant's abstract): The overall objective of the proposed research is to understand the mechanisms of inheritance of mitochondrial DNA (mtDNA) using the budding yeast S. cerevisiae, as a model organism. The proposed studies will combine genetic, biochemical, molecular, and cell biological approaches to identify and characterize the various components that contribute to the faithful transmission of mtDNA during vegetative growth. To these ends, investigators propose three specific aims: 1) To complete the detailed biochemical characterization of mtDNA-protein complexes (nucleoids) which are the segregating units of mtDNA. The goal is to identify by crosslinking procedures the major proteins interacting with mtDNA and to determine how these proteins contribute to the organization and propagation of the mitochondrial genome. 2) To analyze the functions of novel proteins and pathways required for mtDNA transactions. For example, the investigators will expand on the findings that the mitochondrial:chaperone, Hsp60, and some mitochondrial proteins whose expression is under general amino acid control, which they have found to be associated with mtDNA, influence mtDNA inheritance. 3) To analyze cis- and trans-acting elements controlling mtDNA replication and transmission in petite and wild-type strains. These studies will focus on the role of putative origins of replication (ori elements) in the phenomenon of hypersuppressiveness, the role of ori elements in the replication and transmission of wild-type mtDNA and the characterization of an activity that initiates rolling replication from an ori element. How cells transmit their mtDNA is fundamental and applies to almost all eukaryotic cells. It is now clear that a number of inherited disorders involve aspects of the segregation of mutant and wild-type mtDNAs. The investigators have developed a tractable experimental system in which to investigate these important issues.