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Science 7 July 2000:
Vol. 289. no. 5476, pp. 77 - 85
DOI: 10.1126/science.289.5476.77
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Research Articles

Three-Dimensional Structure of the Tn5 Synaptic Complex Transposition Intermediate

Douglas R. Davies, Igor Y. Goryshin, William S. Reznikoff, Ivan Rayment *

Genomic evolution has been profoundly influenced by DNA transposition, a process whereby defined DNA segments move freely about the genome. Transposition is mediated by transposases, and similar events are catalyzed by retroviral integrases such as human immunodeficiency virus-1 (HIV-1) integrase. Understanding how these proteins interact with DNA is central to understanding the molecular basis of transposition. We report the three-dimensional structure of prokaryotic Tn5 transposase complexed with Tn5 transposon end DNA determined to 2.3 angstrom resolution. The molecular assembly is dimeric, where each double-stranded DNA molecule is bound by both protein subunits, orienting the transposon ends into the active sites. This structure provides a molecular framework for understanding many aspects of transposition, including the binding of transposon end DNA by one subunit and cleavage by a second, cleavage of two strands of DNA by a single active site via a hairpin intermediate, and strand transfer into target DNA.

Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
*   To whom correspondence may be addressed. E-mail: ivan_rayment{at}biochem.wisc.edu

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