Molecular Model for the Transposition and Replication of Bacteriophage Mu and other

A series of molecular events will explain how genetic elements can transpose from one DNA site to another, generate a short oligonucleotide duplication at both ends of the new insertion site, and replicate in the transposition process. These events include the formation of recombinant molecules which have been postulated to be intermediates in the transposition process. The model explains how the replication of bacteriophage Mu is obligatorily associated with movement to new genetic sites. It postulates that all transposable elements replicate in the transposition process so that they remain at their original site while moving to new sites. According to this model, the mechanism of transposition is very different from the insertion and excision of bacteriophage X. Recent research on transposable elements in bacteria has provided important insights into the role of nonhomologous recombination in genetic rearrangements (1-4). These elements include small insertion sequences (IS elements), transposable resistance determinants (Tn elements), and bacteriophage Mu (3). There are detailed differences in the genetic behavior of these various elements (such as differences in specificity of site selection for insertion), but there is a consensus that they all share underlying recombination mechanisms (3, 5). Although this consensus originally included the bacteriophage X (cf. refs. 3 and 4), the considerations elaborated below argue that phage Mu and other transposable elements differ radically from the elegant and simple X model (6, 7). The mechanisms by which transposable elements move from one genetic site to another are still unknown. However, there has been a rapid accumulation of information about the structural consequences of transposition events, the genetic control of transposition, and the replication of bacteriophage Mu from work in many laboratories. While some of this information is not yet based on completely unambiguous data, the outlines appear sufficiently clear to propose a partially detailed molecular model to explain the transposition process. This model also explains how phage Mu replicates. Its justification draws examples from work on various elements (particularly Mu, IS1, Tn3, and Tn5) on the assumption that they are all mechanistically equivalent as far as the details of the present model go. This proposal does not address the question of site selection for transposition events and specifically deals only with events that occur after an initial donor-target complex has been formed. OBSERVATIONS TO BE EXPLAINED A model for the mechanism of transposition and replication of phage Mu and the insertion of other transposable elements should be able to explain the following observations. (i) Insertion of a transposable element into a genetic site B