A human XRCC4–XLF complex bridges DNA
Open Access
- 27 January 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 40 (4), 1868-1878
- https://doi.org/10.1093/nar/gks022
Abstract
DNA double-strand breaks pose a significant threat to cell survival and must be repaired. In higher eukaryotes, such damage is repaired efficiently by non-homologous end joining (NHEJ). Within this pathway, XRCC4 and XLF fulfill key roles required for end joining. Using DNA-binding and -bridging assays, combined with direct visualization, we present evidence for how XRCC4–XLF complexes robustly bridge DNA molecules. This unanticipated, DNA Ligase IV-independent bridging activity by XRCC4–XLF suggests an early role for this complex during end joining, in addition to its more well-established later functions. Mutational analysis of the XRCC4–XLF C-terminal tail regions further identifies specialized functions in complex formation and interaction with DNA and DNA Ligase IV. Based on these data and the crystal structure of an extended protein filament of XRCC4–XLF at 3.94 Å, a model for XRCC4–XLF complex function in NHEJ is presented.This publication has 53 references indexed in Scilit:
- Functional significance of the interaction with Ku in DNA double-strand break recognition of XLFFEBS Letters, 2011
- ATM damage response and XLF repair factor are functionally redundant in joining DNA breaksNature, 2010
- A structural model for regulation of NHEJ by DNA-PKcs autophosphorylationDNA Repair, 2010
- XLF Regulates Filament Architecture of the XRCC4·Ligase IV ComplexStructure, 2010
- Super-resolution biomolecular crystallography with low-resolution dataNature, 2010
- Version 1.2 of the Crystallography and NMR systemNature Protocols, 2007
- Inference of Macromolecular Assemblies from Crystalline StateJournal of Molecular Biology, 2007
- Crystal structure of a Rad51 filamentNature Structural & Molecular Biology, 2004
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997
- Characterization of complexes between recA protein and duplex DNA by electron microscopyJournal of Molecular Biology, 1982