Wu, Q orcid.org/0000-0002-6948-7043, Liang, S, Ochi, T et al. (3 more authors) (2019) Understanding the structure and role of DNA-PK in NHEJ: How X-ray diffraction and cryo-EM contribute in complementary ways. Progress in Biophysics and Molecular Biology, 147. pp. 26-32. ISSN 0079-6107
Abstract
DNA double-strand breaks (DSBs), generated by ionizing radiation, reactive oxygen species and DNA replication across nicks, are the most severe DNA damage in eukaryotic cells. Non-Homologous End Joining repairs DNA double-strand breaks directly without a template and so can take place at any point in the cell cycle. Ku70/80 heterodimers rapidly assemble around broken DNA ends, allowing DNA-PKcs, the catalytic subunit of DNA-dependent protein kinase, to be recruited and facilitating synapsis of broken DNA ends. This then provides a stage for end-processing and ligation. Here we review progress leading in 2017 to the medium resolution X-ray structure of DNA-PKcs, a single polypeptide chain of 4128 amino acids. This was followed quickly by chain tracing of cryo-EM structures of DNA-PKcs in complex with Ku and DNA. We discuss how combination of structural information from X-ray and cryo-EM studies can produce a working model for complex multicomponent molecular assemblies such as those found in DNA-double-strand-break repair.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Published by Elsevier Ltd. This is an author produced version of an article published in Progress in Biophysics and Molecular Biology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | DNA-PK; DNA-PKcs; Ku70/80; NHEJ; DSBs; X-ray crystallography; Cryo-EM; DNA repair |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Jun 2020 12:17 |
Last Modified: | 24 Jun 2020 12:17 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.pbiomolbio.2019.03.007 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:162233 |
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Filename: DNA-PKcs_Review_PBMB_Manuscript and Supplementary_12March2019.pdf
Licence: CC-BY-NC-ND 4.0