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Structural insights into the role of domain flexibility in human DNA ligase IV.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Ochi, Takashi 
Wu, Qian 
Chirgadze, Dimitri Y 
Grossmann, J Günter 
Bolanos-Garcia, Victor M 

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.

Description

Keywords

Catalytic Domain, Chromatography, Gel, DNA, DNA Breaks, Double-Stranded, DNA Ligase ATP, DNA Ligases, DNA Nucleotidyltransferases, DNA Repair, DNA Repair Enzymes, DNA-Binding Proteins, Escherichia coli, Humans, Models, Molecular, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Recombinant Proteins, Scattering, Small Angle, X-Ray Diffraction

Journal Title

Structure

Conference Name

Journal ISSN

0969-2126
1878-4186

Volume Title

20

Publisher

Elsevier BV