Mechanism of DNA loading by the DNA repair helicase XPD
Open Access
- 20 February 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 44 (6), 2806-2815
- https://doi.org/10.1093/nar/gkw102
Abstract
The xeroderma pigmentosum group D (XPD) helicase is a component of the transcription factor IIH complex in eukaryotes and plays an essential role in DNA repair in the nucleotide excision repair pathway. XPD is a 5′ to 3′ helicase with an essential iron–sulfur cluster. Structural and biochemical studies of the monomeric archaeal XPD homologues have aided a mechanistic understanding of this important class of helicase, but several important questions remain open. In particular, the mechanism for DNA loading, which is assumed to require large protein conformational change, is not fully understood. Here, DNA binding by the archaeal XPD helicase from Thermoplasma acidophilum has been investigated using a combination of crystallography, cross-linking, modified substrates and biochemical assays. The data are consistent with an initial tight binding of ssDNA to helicase domain 2, followed by transient opening of the interface between the Arch and 4FeS domains, allowing access to a second binding site on helicase domain 1 that directs DNA through the pore. A crystal structure of XPD from Sulfolobus acidocaldiarius that lacks helicase domain 2 has an otherwise unperturbed structure, emphasizing the stability of the interface between the Arch and 4FeS domains in XPD.Keywords
This publication has 49 references indexed in Scilit:
- DNA Quality Control by a Lesion Sensor Pocket of the Xeroderma Pigmentosum Group D Helicase Subunit of TFIIHCurrent Biology, 2013
- DNA charge transport as a first step in coordinating the detection of lesions by repair proteinsProceedings of the National Academy of Sciences of the United States of America, 2012
- Regulation of translocation polarity by helicase domain 1 in SF2B helicasesThe EMBO Journal, 2011
- Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocationThe EMBO Journal, 2011
- ATP-Stimulated, DNA-Mediated Redox Signaling by XPD, a DNA Repair and Transcription HelicaseJournal of the American Chemical Society, 2011
- XPB and XPD helicases in TFIIH orchestrate DNA duplex opening and damage verification to coordinate repair with transcription and cell cycle via CAK kinaseDNA Repair, 2011
- The helicase XPD unwinds bubble structures and is not stalled by DNA lesions removed by the nucleotide excision repair pathwayNucleic Acids Research, 2009
- A simple and efficient expression and purification system using two newly constructed vectorsProtein Expression and Purification, 2008
- XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD MutationsCell, 2008
- Structure of the DNA Repair Helicase XPDCell, 2008