(bacteriophage Mu/transposable genetic elements/integrative replication/DNA amplification/chromosomal translocations)

Bacteriophage Mu and many other transposable elements undergo transposition by a process that involves replica- tion of the element. We describe here a mechanism by which such integrative replication may take place. We have examined electron microscopically the DNA structures generated in host cells after Mu induction and have deduced the following steps in the trans- position process. (i) Association. A protein-mediated association is brought about between the transposable element and the target DNA. (ii) Attachment. One end of the element is nicked and at- tached to a site that undergoes a double-stranded cleavage. (iii) Roll-in replication. While one strand of the target DNA is linked to the nicked strand of the element, the complementary strand of the target DNA is used as a primer for replication into the element such that the replicating DNA is threaded through the replication complex. (iv) Roll-in termination. When the distal end of the ele- ment arrives at the replication complex, replication is terminated. The roll-in replication mechanism can also explain laying down of tandem repeats-i.e., amplification of circular DNA sequences. It has become evident in the last few years that spatial arrange- ments of genetic material may undergo frequent changes both in prokaryotes and eukaryotes. Specific DNA sequences, called "transposable elements," are the primary mediators of such rearrangements (see ref. 1). Studies on bacteriophage Mu, a giant transposable element, suggested that the mechanism of transposition may involve rep- lication of the element (2). The general model of integration de- veloped from these studies can be summarized in the scheme -~~~~~~~~~- *'"b4W 4 X. ~