DNA translocation mechanism of an XPD family helicase

Abstract
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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

1. Cheng K
2. Wigley DB
(2018) Diffraction data from DNA translocation mechanism of an XPD family helicase
Protein Data Bank, 6FWR.

http://www.rcsb.org/structure/6FWR
1. Cheng K
2. Wigley DB
(2018) Diffraction data from DNA translocation mechanism of an XPD family helicase
Protein Data Bank, 6FWS.

http://www.rcsb.org/structure/6FWS

Article and author information

Author details

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.
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.

"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.

Copyright

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.