title: Replisome speed determines the efficiency of the Tus-Ter replication termination barrier.
abstract: In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a 'replication fork trap' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes.
authors: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
authors: Mohamed M
authors: MM
authors: Elshenawy
authors: Centre for Medical &Molecular Bioscience, Illawarra Health &Medical Research Institute and University of Wollongong, New South Wales 2522, Australia.
authors: Slobodan
authors: S
authors: Jergic
authors: Centre for Medical &Molecular Bioscience, Illawarra Health &Medical Research Institute and University of Wollongong, New South Wales 2522, Australia.
authors: Zhi-Qiang
authors: ZQ
authors: Xu
authors: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
authors: Mohamed A
authors: MA
authors: Sobhy
authors: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
authors: Masateru
authors: M
authors: Takahashi
authors: Centre for Medical &Molecular Bioscience, Illawarra Health &Medical Research Institute and University of Wollongong, New South Wales 2522, Australia.
authors: Aaron J
authors: AJ
authors: Oakley
authors: Centre for Medical &Molecular Bioscience, Illawarra Health &Medical Research Institute and University of Wollongong, New South Wales 2522, Australia.
authors: Nicholas E
authors: NE
authors: Dixon
authors: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
authors: Samir M
authors: SM
authors: Hamdan
mesh_terms: D001483:Base Sequence; D001667:Binding, Competitive; D002876:Chromosomes, Bacterial / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D009068:Movement; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D020349:Surface Plasmon Resonance; D013997:Time Factors; D000099272:Replisomes
chemical_list: D004259:DNA-Directed DNA Polymerase; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D000099272:Replisomes; C489236:tus protein, E coli