Visualizing Mu transposition: assembling the puzzle pieces

Mobile genetic elements, once a curiosity of maize genetics, are now known to be remarkably prevalent in the genomes of organisms ranging from pathogenic bacteria to humans. The varied consequences of these elements include the alteration of gene expression and the spread of drug resistance genes among bacteria. Additionally, many viruses and bacteriophages that covalently integrate their own genome into their hosts' do so by mechanisms similar to those used by more domesticated mobile elements that do not normally leave the cell (for review, see Curcio and Derbyshire 2003).

Bacteriophage Mu was the first transposition system studied in vitro, and has in many ways served as a paradigm for understanding the mechanisms of mobile DNA elements (Chaconas and Harshey 2002). In this issue of Genes & Development, Chaconas, Ottensmeyer, and colleagues (Yuan et al. 2005) present an electron microscopy-based 3D model of the protein–DNA complex responsible for Mu transposition (the transpososome). This model not only ties together years of accumulated biochemical and structural data, but also provides interesting new insights.

Mu is a member of the first characterized and perhaps most well studied family of mobile elements, often referred to as the “classical DNA transposons” or the “DDE transposons.” The latter name reflects the conserved active sites of the element-encoded transposase enzymes, which contain three carboxylate side chains that bind catalytic Mg⁺⁺ ions (Mizuuchi and Baker 2002). This large family includes the bacterial transposons Tn5, Tn7, and Tn10 as well as phage Mu, which is covalently inserted into the host genome and, in lytic phase, replicates via a massive burst of transposition. The family can also be extended to include retroviruses such as HIV, whose integration is catalyzed by an enzyme closely related to the DDE transposases.

A generalized pathway for the transposition of these elements is …