TY - JOUR
T1 - What is all this fuss about Tus?
T2 - Comparison of recent findings from biophysical and biochemical experiments
AU - Berghuis, Bojk
AU - Raducanu, Vlad-Stefan
AU - Elshenawy, Mohamed M.
AU - Jergic, Slobodan
AU - Depken, Martin
AU - Dixon, NE
AU - Hamdan, Samir M.
AU - Dekker, Nynke
PY - 2017/11/6
Y1 - 2017/11/6
N2 - 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.
AB - 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.
KW - DNA–protein interactions
KW - DNA replication
KW - prokaryotic replication
KW - replication termination
KW - replisome
KW - Tus–Ter
KW - single-molecule techniques
KW - magnetic tweezers
UR - http://resolver.tudelft.nl/uuid:5940a265-aeb4-46d3-a90b-3e05a25d1279
U2 - 10.1080/10409238.2017.1394264
DO - 10.1080/10409238.2017.1394264
M3 - Article
SN - 1040-9238
SP - 1
EP - 15
JO - Critical Reviews in Biochemistry and Molecular Biology
JF - Critical Reviews in Biochemistry and Molecular Biology
ER -