Structural Biology of DNA Repair: Spatial Organisation of the Multicomponent Complexes of Nonhomologous End Joining. (25th August 2010)

• Record Type: Journal Article
• Authors: Ochi, Takashi; Sibanda, Bancinyane Lynn; Wu, Qian; Chirgadze, Dimitri Y.; Bolanos-Garcia, Victor M.; Blundell, Tom L.
• Other Names: Basu Ashis Academic Editor.
• Is Part Of: Journal of nucleic acids. Volume 2010(2010)
• Publication Date: 2010-08-25
• Subjects: Nucleic acids -- Periodicals; 572.805
• DOI: 10.4061/2010/621695
• Languages: English
• ISSNs: 2090-0201

Abstract

Abstract : Nonhomologous end joining (NHEJ) plays a major role in double-strand break DNA repair, which involves a series of steps mediated by multiprotein complexes. A ring-shaped Ku70/Ku80 heterodimer forms first at broken DNA ends, DNA-dependent protein kinase catalytic subunit (DNA-PKcs) binds to mediate synapsis and nucleases process DNA overhangs. DNA ligase IV (LigIV) is recruited as a complex with XRCC4 for ligation, with XLF/Cernunnos, playing a role in enhancing activity of LigIV. We describe how a combination of methods—X-ray crystallography, electron microscopy and small angle X-ray scattering—can give insights into the transient multicomponent complexes that mediate NHEJ. We first consider the organisation of DNA-PKcs/Ku70/Ku80/DNA complex (DNA-PK) and then discuss emerging evidence concerning LigIV/XRCC4/XLF/DNA and higher-order complexes. We conclude by discussing roles of multiprotein systems in maintaining high signal-to-noise and the value of structural studies in developing new therapies in oncology and elsewhere.