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| Title | Understanding the structure and role of DNA-PK in NHEJ: How X-ray diffraction and cryo-EM contribute in complementary ways. |
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| Journal, issue, pages | Prog Biophys Mol Biol, Vol. 147, Page 26-32, Year 2019 |
| Publish date | Apr 20, 2019 |
Authors | Qian Wu / Shikang Liang / Takashi Ochi / Dimitri Y Chirgadze / Juha T Huiskonen / Tom L Blundell / ![]() |
| PubMed 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 ...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. |
External links | Prog Biophys Mol Biol / PubMed:31014919 |
| Methods | EM (single particle) |
| Resolution | 5.7 Å |
| Structure data | ![]() EMDB-4425: |
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