DNA translocation mechanism of an XPD family helicase

  1. Kaiying Cheng
  2. Dale B Wigley  Is a corresponding author
  1. Imperial College London, United Kingdom

Abstract

The XPD family of helicases, that includes human disease-related FANCJ, DDX11 and RTEL1, are Superfamily 2 helicases that contain an iron-sulphur cluster domain, translocate on ssDNA in a 5'-3' direction and play important roles in genome stability. Consequently, mutations in several of these family members in eukaryotes cause human diseases. Family members in bacteria, such as the DinG helicase from Escherichia coli, are also involved in DNA repair. Here we present crystal structures of complexes of DinG bound to single-stranded DNA (ssDNA) in the presence and absence of an ATP analogue (ADP•BeF3), that suggest a mechanism for 5'-3' translocation along the ssDNA substrate. This proposed mechanism has implications for how those enzymes of the XPD family that recognise bulky DNA lesionsmight stall at these as the first step in initiating DNA repair. Biochemical data reveal roles for conserved residues that are mutated in human diseases.

Data availability

Diffraction data have been deposited in PDB under the accession codes 6FWR and 6FWS.

The following data sets were generated

Article and author information

Author details

  1. Kaiying Cheng

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Dale B Wigley

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    For correspondence
    d.wigley@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0786-6726

Funding

Medical Research Council

  • Dale B Wigley

Cancer Research UK

  • Dale B Wigley

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

Reviewing Editor

  1. James M Berger, Johns Hopkins University School of Medicine, United States

Version history

  1. Received: September 27, 2018
  2. Accepted: December 5, 2018
  3. Accepted Manuscript published: December 6, 2018 (version 1)
  4. Version of Record published: December 19, 2018 (version 2)

Copyright

© 2018, Cheng & Wigley

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. Kaiying Cheng
  2. Dale B Wigley
(2018)
DNA translocation mechanism of an XPD family helicase
eLife 7:e42400.
https://doi.org/10.7554/eLife.42400

Share this article

https://doi.org/10.7554/eLife.42400

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