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Eukaryotic genomes are very complex but dynamic structures. We are studying this dynamic flexibility and the role of oxidative DNA damage in aging. As an experimental model system we employ the dynamic L2Hs elements in human DNA and in recombinant DNA constructs. The L2Hs sequences have undergone amplifications and rearrangements in the evolution of human genomes. They are useful in "DNA fingerprinting" individual humans and for following the process of genomic DNA differentiation during the development of cell lineages in embryogenesis and tumor oncogenesis. and in tracking the effects of genomic damage. These properties are related to the potential of L2Hs elements to form unusual DNA structures and to affect the structure of adjacent chromosomal sequences. In a related project, a prokaryotic "replicative evolution" model system has been developed to study the stability of a recombinant plasmid containing these dynamic sequences during normal growth and in response to environmental oxidative challenge.