1. Biochemistry and Chemical Biology
  2. Chromosomes and Gene Expression

Competitive binding of MatP and topoisomerase IV to the MukB hinge domain

  1. Gemma LM Fisher
  2. Jani R Bolla
  3. Karthik V Rajasekar
  4. Jarno Mäkelä
  5. Rachel Baker
  6. Man Zhou
  7. Josh P Prince
  8. Mathew Stracy
  9. Carol V Robinson
  10. Lidia K Arciszewska
  11. David J Sherratt  Is a corresponding author
  1. London Institute of Medical Sciences, United Kingdom
  2. University of Oxford, United Kingdom
  3. Stanford University, United States
  4. University of Cambridge, United Kingdom
https://doi.org/10.7554/eLife.70444
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  1. Gemma LM Fisher
  2. Jani R Bolla
  3. Karthik V Rajasekar
  4. Jarno Mäkelä
  5. Rachel Baker
  6. Man Zhou
  7. Josh P Prince
  8. Mathew Stracy
  9. Carol V Robinson
  10. Lidia K Arciszewska
  11. David J Sherratt
(2021)
Competitive binding of MatP and topoisomerase IV to the MukB hinge domain
eLife 10:e70444.
https://doi.org/10.7554/eLife.70444
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  3. Download .RIS

Abstract

Structural Maintenance of Chromosomes (SMC) complexes have ubiquitous roles in compacting DNA linearly, thereby promoting chromosome organization-segregation. Interaction between the Escherichia coli SMC complex, MukBEF, and matS-bound MatP in the chromosome replication termination region, ter, results in depletion of MukBEF from ter, a process essential for efficient daughter chromosome individualisation and for preferential association of MukBEF with the replication origin region. Chromosome-associated MukBEF complexes also interact with topoisomerase IV (ParC2E2), so that their chromosome distribution mirrors that of MukBEF. We demonstrate that MatP and ParC have an overlapping binding interface on the MukB hinge, leading to their mutually exclusive binding, which occurs with the same dimer to dimer stoichiometry. Furthermore, we show that matS DNA competes with the MukB hinge for MatP binding. Cells expressing MukBEF complexes that are mutated at the ParC/MatP binding interface are impaired in ParC binding and have a mild defect in MukBEF function. The data highlight competitive binding as a means of globally regulating MukBEF-topoisomerase IV activity in space and time.

Data availability

Source data files have been provided for all gel-based figures. Source data files for other assays have been included where indicated. All custom MATLAB scripts are provided as Source Code 1. All code used is previously published and also available via the cited reference(s). All reagents are available upon reasonable request.

Article and author information

Author details

  1. Gemma LM Fisher

    School of Biochemistry, London Institute of Medical Sciences, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  2. Jani R Bolla

    Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4346-182X

  3. Karthik V Rajasekar

    Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Jarno Mäkelä

    Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Rachel Baker

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Man Zhou

    University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  7. Josh P Prince

    Epigenetics, London Institute of Medical Sciences, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0877-7538

  8. Mathew Stracy

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  9. Carol V Robinson

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  10. Lidia K Arciszewska

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0252-4874

  11. David J Sherratt

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    david.sherratt@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2104-5430

Funding

Wellcome Trust (200782/Z/16/Z)

  • David J Sherratt

Medical Research Council (MR/N020413/1)

  • Carol V Robinson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Fisher et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Gemma LM Fisher
  2. Jani R Bolla
  3. Karthik V Rajasekar
  4. Jarno Mäkelä
  5. Rachel Baker
  6. Man Zhou
  7. Josh P Prince
  8. Mathew Stracy
  9. Carol V Robinson
  10. Lidia K Arciszewska
  11. David J Sherratt
(2021)
Competitive binding of MatP and topoisomerase IV to the MukB hinge domain
eLife 10:e70444.
https://doi.org/10.7554/eLife.70444

Share this article

https://doi.org/10.7554/eLife.70444

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