Structure of Kinetoplast DNA

锥虫的动泡体DNA(KDNA)具有一种非常不寻常的结构，由数千个相连的DNA环组成，称为上环和微环。此外，这些环状DNA分子似乎在细胞周期控制下复制，特别是微环，根据它们是否被复制而被分离到kDNA网络的不同区域。将研究不同复制程度下kDNA网络结构的组织，以此作为阐明控制单个网络精确复制的机制的一种手段。防止复制的微环最终共价闭合，从而防止其在子网络分离之前第二次复制的机制特别令人感兴趣。还将探索最大环连接到网络的方式，以及微环的弯曲螺旋DNA片段在将复制的微环靶向网络的特定结构域中的可能作用。此外，还将寻找可能与体内DNA网络的缩合和组织有关的蛋白质。真核细胞中DNA复制的机制以及复制与细胞周期的协调是生物学中的基本问题。动泡体DNA包含两种不同类型的复制子，即小环和上环，与哺乳动物线粒体DNA不同，这两种复制子都与细胞周期相协调地复制。此外，调控动泡体复制的基因很可能是在细胞核中编码的，可能与控制核DNA合成的基因相似或相关。因此，动泡体DNA系统提供了一个了解真核细胞生长和分裂的基本方面的机会。

Kinetoplast DNA (kDNA) of trypanosomes has a highly unusual structural organization consisting of thousands of catenated DNA circles termed maxicircles and minicircles. In addition, these circular DNA molecules appear to replicate under cell cycle control and minicircles, in particular, are segregated into distinct domains of the kDNA network depending on whether or not they have been replicated. The structural organization of kDNA networks at different extents of replication will be investigated as a means of elucidating the mechanisms controlling the precise duplication of individual networks. The mechanisms that prevent the final covalent closure of duplicated minicircles and thereby prevent their replication a second time prior to segregation of daughter networks is of a particular interest. The manner in which maxicircles are catenated to the network and the possible role of bent helical DNA segments of minicircles in targeting duplicated minicircles to a specific domain of the network will also be explored. Additionally a search will be made for proteins that may be involved in the condensation and organization of the DNA network in vivo. The mechanism of DNA replication in eukaryotic cells and the coordination of replication with the cell cycle are fundamental problems in biology. Kinetoplast DNA contains two distinct types of replicons, minicircles and maxicircles, both of which, unlike mammalian mitochondrial DNA, are replicated coordinately with the cell cycle. In addition, the genes that regulate kinetoplast replication are likely to be encoded in the nucleus and may be similar or related to the genes controlling nuclear DNA synthesis. Thus, the kinetoplast DNA system offers an opportunity to understand fundamental aspects of the growth and division of eukaryotic cells.