What is all this fuss about Tus? Comparison of recent findings from biophysical and biochemical experiments
Synchronizing the convergence of the two-oppositely moving DNA replication machineries at specific termination sites is a tightly coordinated process in bacteria. In Escherichia coli, a "replication fork trap"-found within a chromosomal region where forks are allowed to enter but not leave-is set by the protein-DNA roadblock Tus-Ter. The exact sequence of events by which Tus-Ter blocks replisomes approaching from one direction but not the other has been the subject of controversy for many decades. Specific protein-protein interactions between the nonpermissive face of Tus and the approaching helicase were challenged by biochemical and structural studies. These studies show that it is the helicase-induced strand separation that triggers the formation of new Tus-Ter interactions at the nonpermissive face-interactions that result in a highly stable "locked" complex. This controversy recently gained renewed attention as three single-molecule-based studies scrutinized this elusive Tus-Ter mechanism-leading to new findings and refinement of existing models, but also generating new questions. Here, we discuss and compare the findings of each of the single-molecule studies to find their common ground, pinpoint the crucial differences that remain, and push the understanding of this bipartite DNA-protein system further.
Berghuis, B. A., Raducanu, V., Elshenawy, M. M., Jergic, S., Depken, M., Dixon, N. E., Hamdan, S. M. & Dekker, N. H. (2018). What is all this fuss about Tus? Comparison of recent findings from biophysical and biochemical experiments. Critical Reviews in Biochemistry and Molecular Biology, 53 (1), 49-63.