SAP domain forms a flexible part of DNA aperture in Ku70/80
| Autor: | Roland Beckmann, Thanh Binh Nguyen, Zdeněk Kukačka, Amanda K. Chaplin, Aleš Hnízda, Petr Novák, Petr Tesina, Lukas Kater, Tom L. Blundell, David B. Ascher |
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| Přispěvatelé: | Hnízda, Aleš [0000-0002-1521-4453], Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DNA double‐strand break DNA End-Joining Repair Protein Conformation Protein domain Protein Data Bank (RCSB PDB) Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein structure Protein Domains Humans A-DNA DNA Breaks Double-Stranded Molecular Biology Ku Autoantigen integrative structural biology Physics Original Articles Cell Biology computer.file_format DNA Protein Data Bank SAP domain nonhomologous end joining Non-homologous end joining Ku70/80 030104 developmental biology chemistry 030220 oncology & carcinogenesis DNA double-strand break Biophysics Original Article computer |
| Zdroj: | The Febs Journal |
| Popis: | Funder: Victorian Government Funder: BBSRC Nonhomologous end joining (NHEJ) is a DNA repair mechanism that religates double-strand DNA breaks to maintain genomic integrity during the entire cell cycle. The Ku70/80 complex recognizes DNA breaks and serves as an essential hub for recruitment of NHEJ components. Here, we describe intramolecular interactions of the Ku70 C-terminal domain, known as the SAP domain. Using single-particle cryo-electron microscopy, mass spectrometric analysis of intermolecular cross-linking and molecular modelling simulations, we captured variable positions of the SAP domain depending on DNA binding. The first position was localized at the DNA aperture in the Ku70/80 apo form but was not observed in the DNA-bound state. The second position, which was observed in both apo and DNA-bound states, was found below the DNA aperture, close to the helical arm of Ku70. The localization of the SAP domain in the DNA aperture suggests a function as a flexible entry gate for broken DNA. DATABASES: EM maps have been deposited in EMDB (EMD-11933). Coordinates have been deposited in Protein Data Bank (PDB 7AXZ). Other data are available from corresponding authors upon a request. |
| Databáze: | OpenAIRE |
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