Quality Control in Mu DNA Transposition

Abstract

The emerging picture of DNA transposition is one of both striking similarities and differences among elements. On the biochemical level it is clear that the transposition mechanism is highly conserved. In all cases, transposition is initiated by cleavage at the 3′ ends of the transposon, and a transesterification reaction splices these ends into a target DNA. The mechanistic commonality is highlighted by the similarity of structures of the catalytic domain of Mu transposase, HIV-1 integrase, and ASV integrase (reviewed inRice et al. 1996xRice, P, Craigie, R, and Davies, D.R. Curr. Opin. Struct. Biol. 1996; 6: 76–83Crossref | PubMed | Scopus (166)See all ReferencesRice et al. 1996). Although the Mu transposase and retroviral integrases share very little common primary sequence, the three dimensional structures of the catalytic domain are very similar. We may safely conclude that the mechanism of chemical catalysis is highly conserved.Although the series of DNA cutting and joining events are very similar among transposons, the transposase proteins themselves and their DNA sites for recognition are quite diverse in organization. Many transposons have a single transposase binding site at their termini, others like Mu and Tn 7 have a complex array of sites. In the case of Tn 7, transposase consists of at least four different polypeptides. Retroviral integrases appear to rely on the nucleoprotein structure of the viral core to assemble on the viral DNA ends. Unlike typical transposases, their binding affinity for viral DNA ends is not significantly greater than that for nonspecific DNA.Transposons and their cousins have clearly evolved different strategies to suit their individual lifestyles. Although the nucleoprotein architecture of many related elements clearly can not be identical to Mu because the building blocks are not conserved, some features of the Mu architectural regulation may be common among transposable genetic elements. The requirement for a pair of DNA sites to undergo synapsis before the protein factors can be correctly positioned for catalysis provides an effective way of avoiding unproductive or abortive recombination events. Cooperation among protein monomers to form a catalytic unit may be a common mechanism to ensure that DNA cleavage and ligation reactions are properly coordinated, as has been proposed for Flp recombinase (Chen et al. 1992xChen, J.-W, Lee, J, and Jayaram, M. Cell. 1992; 69: 647–658Abstract | Full Text PDF | PubMed | Scopus (105)See all ReferencesChen et al. 1992) and Mu transposase (Yang et al. 1995xYang, J.-Y, Kim, K, Jayaram, M, and Harshey, R.M. EMBO J. 1995; 14: 2374–2384PubMedSee all ReferencesYang et al. 1995).Mu transposition must occur with extraordinarily high efficiency and fidelity during lytic growth, yet it must be totally shut down during lysogeny. The sophisticated regulatory system revealed by recent studies may have resulted from these disparate selection pressures operating at different stages of the replication cycle. It is a paramount example of the use of specialized nucleoprotein structures to regulate biochemical reactions with high precision, as discussed by Echols 1986xEchols, H. Science. 1986; 223: 1050–1056CrossrefSee all ReferencesEchols 1986.