Research output: Contribution to journal › Article › peer-review
DNA complexes with human apurinic/apyrimidinic endonuclease 1 : structural insights revealed by pulsed dipolar EPR with orthogonal spin labeling. / Krumkacheva, Olesya A.; Shevelev, Georgiy Yu; Lomzov, Alexander A. et al.
In: Nucleic Acids Research, Vol. 47, No. 15, 05.09.2019, p. 7767-7780.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - DNA complexes with human apurinic/apyrimidinic endonuclease 1
T2 - structural insights revealed by pulsed dipolar EPR with orthogonal spin labeling
AU - Krumkacheva, Olesya A.
AU - Shevelev, Georgiy Yu
AU - Lomzov, Alexander A.
AU - Dyrkheeva, Nadezhda S.
AU - Kuzhelev, Andrey A.
AU - Koval, Vladimir V.
AU - Tormyshev, Victor M.
AU - Polienko, Yuliya F.
AU - Fedin, Matvey V.
AU - Pyshnyi, Dmitrii V.
AU - Lavrik, Olga I.
AU - Bagryanskaya, Elena G.
N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2019/9/5
Y1 - 2019/9/5
N2 - A DNA molecule is under continuous influence of endogenous and exogenous damaging factors, which produce a variety of DNA lesions. Apurinic/apyrimidinic sites (abasic or AP sites) are among the most common DNA lesions. In this work, we applied pulse dipolar electron paramagnetic resonance (EPR) spectroscopy in combination with molecular dynamics (MD) simulations to investigate in-depth conformational changes in DNA containing an AP site and in a complex of this DNA with AP endonuclease 1 (APE1). For this purpose, triarylmethyl (TAM)-based spin labels were attached to the 5' ends of an oligonucleotide duplex, and nitroxide spin labels were introduced into APE1. In this way, we created a system that enabled monitoring the conformational changes of the main APE1 substrate by EPR. In addition, we were able to trace substrate-to-product transformation in this system. The use of different (orthogonal) spin labels in the enzyme and in the DNA substrate has a crucial advantage allowing for detailed investigation of local damage and conformational changes in AP-DNA alone and in its complex with APE1.
AB - A DNA molecule is under continuous influence of endogenous and exogenous damaging factors, which produce a variety of DNA lesions. Apurinic/apyrimidinic sites (abasic or AP sites) are among the most common DNA lesions. In this work, we applied pulse dipolar electron paramagnetic resonance (EPR) spectroscopy in combination with molecular dynamics (MD) simulations to investigate in-depth conformational changes in DNA containing an AP site and in a complex of this DNA with AP endonuclease 1 (APE1). For this purpose, triarylmethyl (TAM)-based spin labels were attached to the 5' ends of an oligonucleotide duplex, and nitroxide spin labels were introduced into APE1. In this way, we created a system that enabled monitoring the conformational changes of the main APE1 substrate by EPR. In addition, we were able to trace substrate-to-product transformation in this system. The use of different (orthogonal) spin labels in the enzyme and in the DNA substrate has a crucial advantage allowing for detailed investigation of local damage and conformational changes in AP-DNA alone and in its complex with APE1.
UR - http://www.scopus.com/inward/record.url?scp=85072058932&partnerID=8YFLogxK
U2 - 10.1093/nar/gkz620
DO - 10.1093/nar/gkz620
M3 - Article
C2 - 31329919
VL - 47
SP - 7767
EP - 7780
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 15
ER -
ID: 21451817