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Structural Insights into the Role of Domain Flexibility in Human DNA Ligase IV

DOI: 10.1016/j.str.2012.04.012 DOI Help

Authors: Takashi Ochi (University of Cambridge) , Qian Wu (University of Cambridge) , Dima Chirgadze (University of Cambridge) , J. Guenter Grossmann (University of Liverpool) , Victor M. Bolanos-garcia (Oxford Brookes University) , Tom L. Blundell (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 20 (7) , PAGES 1212 - 1222

State: Published (Approved)
Published: July 2012

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.

Journal Keywords: Dna Ligase Iv; Xrcc4; Xlf; Nhej; Dna Repair

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography

Other Facilities: ESRF

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