DNA translocation mechanism of an XPD family helicase
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.
Article and author information
Author details
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
© 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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