Transposable genetic elements are the generators of a variety of rearrangements which mutate genes and perturb their regulation. These elements promote and regulate their own movement. Their study is important therefore in understanding how the proteins they encode interact with DNA to modify it both by recombining and regulating its genetic potential. Our studies will focus on the model transponson, phage Mu. Mu is unique in being the only transposon whose transposition proteins function efficiently in vitro and are therefore amenable to elaborate biochemical analysis. Mu encodes two mechanisms of DNA transposition- conservative and replicative DNA transposition. We propose to carry out a detailed study of the phage proteins A and B required for both mechanisms of Mu transposition, with a view to understanding structure-function relationships in thes proteins. This would help us understand the molecular details of DNA- protein and protein-protein interactions fundamental to transposition as well as to DNA excision. We also propose to study the 64kDa protein found in infecting Mu DNA. These studies will be important in elucidating the mechanism of conservative DNA transposition. Mu DNA transposition is regulated at many levels. We propose experiments that specifically address the post-transcriptional regulation of A- protein synthesis. We hope to uncover novel ways in which transposases limit their expression and thereby their mutagenic potential.
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