Abstract
Knowledge of the architecture of DNA ligase IV (LigIV) and interactions with XRCC4 and XLF-Cernunnos is necessary for understanding its role in the ligation of double-strand breaks during nonhomologous end joining. Here we report the structure of a subdomain of the nucleotidyltrasferase domain of human LigIV and provide insights into the residues associated with LIG4 syndrome. We use this structural information together with the known structures of the BRCT/XRCC4 complex and those of LigIV orthologs to interpret small-angle X-ray scattering of LigIV in complex with XRCC4 and size exclusion chromatography of LigIV, XRCC4, and XLF-Cernunnos. Our results suggest that the flexibility of the catalytic region is limited in a manner that affects the formation of the LigIV/XRCC4/XLF-Cernunnos complex.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Catalytic Domain
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Chromatography, Gel
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DNA / chemistry*
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DNA / metabolism
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DNA Breaks, Double-Stranded
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DNA Ligase ATP
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DNA Ligases / chemistry*
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DNA Ligases / genetics
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DNA Ligases / metabolism
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DNA Nucleotidyltransferases / chemistry*
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DNA Nucleotidyltransferases / genetics
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DNA Nucleotidyltransferases / metabolism
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DNA Repair Enzymes / chemistry*
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DNA Repair Enzymes / genetics
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DNA Repair Enzymes / metabolism
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DNA Repair*
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Escherichia coli
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Humans
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Models, Molecular
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Scattering, Small Angle
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X-Ray Diffraction
Substances
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DNA-Binding Proteins
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LIG4 protein, human
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NHEJ1 protein, human
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Recombinant Proteins
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XRCC4 protein, human
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DNA
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DNA Nucleotidyltransferases
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DNA Ligases
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DNA Repair Enzymes
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DNA Ligase ATP