Structure of Kinetoplast DNA

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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.