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| Subject Categories: Structural Biology | Genome Stability & Dynamics |
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| The EMBO Journal
(2005) 24, 895–905, doi:10.1038/sj.emboj.7600581 Published online 17 February 2005 |
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| Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition |
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| Matthew Newman1, Judith Murray-Rust1, John Lally1, Jana Rudolf2, Andrew Fadden1, Philip P Knowles1, Malcolm F White2 and Neil Q McDonald1, 3 |
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1 Structural Biology Laboratory, London Research Institute, Cancer Research UK, London, UK 2 Centre for Biomolecular Sciences, University of St Andrews, Fife, UK 3 School of Crystallography, Birkbeck College, London, UK To whom correspondence should be addressed Neil Q McDonald, Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Tel.: +44 207 269 3259; Fax: +44 207 269 3258; E-mail: mcdonald@cancer.org.uk Received 8 October 2004; Accepted 19 January 2005; Published online 17 February 2005. |
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| Abstract |
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| The XPF/Mus81 structure-specific endonucleases cleave double-stranded DNA (dsDNA) within asymmetric branched DNA substrates and play an essential role in nucleotide excision repair, recombination and genome integrity. We report the structure of an archaeal XPF homodimer alone and bound to dsDNA. Superposition of these structures reveals a large domain movement upon binding DNA, indicating how the (HhH)2 domain and the nuclease domain are coupled to allow the recognition of double-stranded/single-stranded DNA junctions. We identify two nonequivalent DNA-binding sites and propose a model in which XPF distorts the 3' flap substrate in order to engage both binding sites and promote strand cleavage. The model rationalises published biochemical data and implies a novel role for the ERCC1 subunit of eukaryotic XPF complexes. |
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| Keywords: archaea, DNA repair, endonuclease, HhH domain, XPF |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSJunctions on the road to cancer Nature Structural & Molecular Biology News and Views (01 Aug 2004) RESEARCHSolution structure and DNA-binding properties of the C-terminal domain of UvrC from E.coli The EMBO Journal Article (15 Nov 2002) The active site of the DNA repair endonuclease XPF?ERCC1 forms a highly conserved nuclease motif The EMBO Journal Article (15 Apr 2002) Recognition of DNA damage by the Rad4 nucleotide excision repair protein Nature Article (04 Oct 2007) Role of ERCC1 in removal of long non-homologous tails during targeted homologous recombination The EMBO Journal Article (16 Oct 2000) |
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