ORGANIZATION, EXPRESSION, AND INHERITANCE OF YEAST MTDNA

描述(改编自申请人的摘要)： 建议的研究是为了了解遗传的机制 以发芽酵母为模型的线粒体DNA(MtDNA) 有机体。拟议的研究将结合遗传学、生化、分子、 以及细胞生物学方法来鉴定和表征各种 有助于线粒体DNA的忠实传输的组件 营养生长。为此，调查人员提出了三个具体目标：1) 完成线粒体DNA-蛋白质的详细生化特性 线粒体DNA的分离单元--复合体(类核)。我们的目标是 用交联法鉴定与线粒体DNA相互作用的主要蛋白质 并确定这些蛋白质如何对组织和 线粒体基因组的繁殖。2)分析小说的功能 线粒体DNA交易所需的蛋白质和途径。例如， 研究人员将进一步研究线粒体：伴侣， HSP60，以及一些表达在普通氨基酸以下的线粒体蛋白 酸控制，他们发现这与线粒体DNA有关，影响 线粒体DNA遗传。3)分析顺式和反式作用元件的控制 线粒体DNA在矮小和野生型菌株中的复制和传播。这些 研究将集中在假定的复制起源(ORI)的作用 因素)在过度压抑现象中，ORI因素的作用 野生型mtDNA的复制和传播及其特性 从ORI元素启动滚动复制的活动。多么 细胞传递线粒体DNA是基本的，几乎适用于所有真核生物 细胞。现在很明显，一些遗传性疾病涉及到以下几个方面 突变型和野生型线粒体DNA的分离。调查人员已经 开发了一个易于处理的实验系统来研究这些 重要的问题。

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.