SAP domain forms a flexible part of DNA aperture in Ku70/80

J 2021

SAP domain forms a flexible part of DNA aperture in Ku70/80

HNIZDA, A., P. TESINA, T.B. NGUYEN, Z. KUKACKA, L. KATER et. al.

Základní údaje

Originální název

SAP domain forms a flexible part of DNA aperture in Ku70/80

Autoři

HNIZDA, A., P. TESINA, T.B. NGUYEN, Z. KUKACKA, L. KATER, A. CHAPLIN, R. BECKMANN, D.B. ASCHER, P. NOVAK a T.L. BLUNDELL

Vydání

FEBS JOURNAL, 2021, 1742-464X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.622

Kód RIV

RIV/00216224:14740/21:00124528

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1111/febs.15732

UT WoS

000618236000001

Klíčová slova anglicky

DNA double‐strand breakintegrative structural biologyKu7080nonhomologous end joiningSAP domain

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 5. 2022 15:06, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

HNIZDA, A., P. TESINA, T.B. NGUYEN, Z. KUKACKA, L. KATER, A. CHAPLIN, R. BECKMANN, D.B. ASCHER, P. NOVAK a T.L. BLUNDELL. SAP domain forms a flexible part of DNA aperture in Ku70/80. FEBS JOURNAL. 2021, roč. 288, č. 14, s. 4382-4393. ISSN 1742-464X. Dostupné z: https://dx.doi.org/10.1111/febs.15732.

@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 a T.L. BLUNDELL. SAP domain forms a flexible part of DNA aperture in Ku70/80. \textit{FEBS JOURNAL}. 2021, roč.~288, č.~14, s.~4382-4393. ISSN~1742-464X. Dostupné z: https://dx.doi.org/10.1111/febs.15732.

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