Letter | Published:

Replisome speed determines the efficiency of the Tus−Ter replication termination barrier

Nature volume 525, pages 394398 (17 September 2015) | Download Citation


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 sites1. Escherichia coli sets a ‘replication fork trap’ that allows the first arriving fork to enter but not to leave the terminus region2,3,4,5. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction3,4,5,6,7. 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 vitro8,9. 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.

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Data deposits

Atomic coordinates and structure factors for the reported crystal structures have been deposited at the Protein Data Bank under accession codes 4XR0 (Tus–UGLT fork), 4XR1 (Tus–TGTA fork), 4XR2 (H144A–WT fork) and 4XR3 (Tus-UGLC).


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We thank A. van Oijen for critical comments and the groups of N. Dekker and S. Patel for helpful discussions. This research was supported by the King Abdullah University of Science and Technology through core funding (to S.M.H.) and a Faculty Initiated Collaborative Award (to S.M.H. and N.E.D.), and by the Australian Research Council (DP0877658 to N.E.D. and A.J.O.; DP0984797 to N.E.D.), including an Australian Professorial Fellowship to N.E.D. and a Future Fellowship (FT0990287) to A.J.O. X-ray crystallographic data were collected at the Australian Synchrotron, Victoria, Australia.

Author information


  1. Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia

    • Mohamed M. Elshenawy
    • , Mohamed A. Sobhy
    • , Masateru Takahashi
    •  & Samir M. Hamdan
  2. Centre for Medical & Molecular Bioscience, Illawarra Health & Medical Research Institute and University of Wollongong, New South Wales 2522, Australia

    • Slobodan Jergic
    • , Zhi-Qiang Xu
    • , Aaron J. Oakley
    •  & Nicholas E. Dixon


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M.M.E. designed and carried out the single-molecule replication assays; M.M.E., M.A.S. and M.T. established the single-molecule replication assays; S.J. designed and carried out SPR measurements; S.J. and Z.-Q.X. isolated proteins; Z.-Q.X. and A.J.O. crystallized complexes, collected X-ray data and refined crystal structures. M.M.E., S.J., N.E.D. and S.M.H. designed the research and wrote the article. All authors analysed the data, discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Nicholas E. Dixon or Samir M. Hamdan.

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