Stable maintenance of an extrachromosomal selfish DNA

描述(申请人提供)：酵母质粒2微米圈提供 一种简单的模型系统来研究良性疾病的分子机制 寄生虫基因组优化其生存策略而不影响 寄主的适合度。质粒的信息内容和组织 基因组的设计是为了使其在种群中保持稳定 所述拷贝数不会对宿主代谢机制造成影响。一 这种高拷贝自繁殖机制的分子成分是一种稳定性 确保复制的质粒分子均匀分布到 细胞分裂过程中的子细胞。两个由质粒编码的蛋白质一起 具有顺式作用的DNA序列(称为STB基因座)，对于 稳定系统正常运行。此外，主机编码的因素可以 有助于均质粒的均分。2微米的圆圈也有 设计了一个放大系统，只有当有 由于偶发的平等隔离失败而导致的副本数量的下降。 扩增是由FLP重组酶(FLP，意为翻转或倒转)介导的 DNA)，其活动将单个复制启动事件转换为 多重复印机构，从而快速恢复份数。 在这个提案中，我们描述了一些实验，这些实验试图阐明 质粒和宿主编码的成分相互作用，建立功能 稳定系统。我们认为，从这一点上总结出的一些原则 这项研究将对人类之间的共生关系产生全球影响 原核生物和真核生物中的寄主-寄生虫基因组。

DESCRIPTION (provided by applicant): The yeast plasmid 2 micron circle provides a simple model system to study the molecular mechanisms by which a 'benign parasite genome' optimizes its survival strategies without compromising the fitness of its host. The informational content and organization of the plasmid genome is designed for its stable maintenance in the population at a steady state copy number that does not strain the host metabolic machinery. One molecular component of this high copy self-propagation mechanism is a stability system that ensures equal distribution of replicated plasmid molecules to daughter cells during cell division. Two plasmid-encoded proteins, together with a cis-acting DNA sequence (called the STB locus), are essential for the normal operation of the stability system. In addition, host encoded factors may contribute towards equipartitioning of plasmids. The 2-micron circle has also devised an amplification system, which comes into operation only when there is a drop in copy number due to an occasional failure in equal segregation. Amplification is mediated by the Flp recombinase (Flp for flipping or inverting DNA), whose activity converts a single replication initiation event into a multiple copying mechanism, thus quickly restoring copy number. In this proposal, we describe experiments that attempt to shed light on how the plasmid and host encoded components interact to establish a functional stability system. We believe that some of the principles gleaned from this study will have global implications in the symbiotic relationships among host-parasite genomes in prokaryotes and eukaryotes.