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@article{1846838,
author = {Hnizda, A. and Tesina, P. and Nguyen, T.B. and Kukacka, Z. and Kater, L. and Chaplin, A. and Beckmann, R. and Ascher, D.B. and Novak, P. and Blundell, T.L.},
article_number = {14},
doi = {http://dx.doi.org/10.1111/febs.15732},
keywords = {DNA double‐strand breakintegrative structural biologyKu7080nonhomologous end joiningSAP domain},
language = {eng},
issn = {1742-464X},
journal = {FEBS JOURNAL},
title = {SAP domain forms a flexible part of DNA aperture in Ku70/80},
url = {https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15732},
volume = {288},
year = {2021}
}
TY - JOUR
ID - 1846838
AU - Hnizda, A. - Tesina, P. - Nguyen, T.B. - Kukacka, Z. - Kater, L. - Chaplin, A. - Beckmann, R. - Ascher, D.B. - Novak, P. - Blundell, T.L.
PY - 2021
TI - SAP domain forms a flexible part of DNA aperture in Ku70/80
JF - FEBS JOURNAL
VL - 288
IS - 14
SP - 4382-4393
EP - 4382-4393
SN - 1742464X
KW - DNA double‐strand breakintegrative structural biologyKu7080nonhomologous end joiningSAP domain
UR - https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15732
N2 - 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 ). Other data are available from corresponding authors upon a request.
ER -
HNIZDA, A., P. TESINA, T.B. NGUYEN, Z. KUKACKA, L. KATER, A. CHAPLIN, R. BECKMANN, D.B. ASCHER, P. NOVAK and T.L. BLUNDELL. SAP domain forms a flexible part of DNA aperture in Ku70/80. \textit{FEBS JOURNAL}. 2021, vol.~288, No~14, p.~4382-4393. ISSN~1742-464X. Available from: https://dx.doi.org/10.1111/febs.15732.
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