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Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway. / Kuznetsova, Alexandra A.; Matveeva, Anna G.; Milov, Alexander D. et al.

In: Nucleic Acids Research, Vol. 46, No. 21, 30.11.2018, p. 11454-11465.

Research output: Contribution to journal › Article › peer-review

Harvard

Kuznetsova, AA, Matveeva, AG, Milov, AD, Vorobjev, YN, Dzuba, SA, Fedorova, OS & Kuznetsov, NA 2018, 'Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway', Nucleic Acids Research, vol. 46, no. 21, pp. 11454-11465. https://doi.org/10.1093/nar/gky912

APA

Kuznetsova, A. A., Matveeva, A. G., Milov, A. D., Vorobjev, Y. N., Dzuba, S. A., Fedorova, O. S., & Kuznetsov, N. A. (2018). Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway. Nucleic Acids Research, 46(21), 11454-11465. https://doi.org/10.1093/nar/gky912

Vancouver

Kuznetsova AA, Matveeva AG, Milov AD, Vorobjev YN, Dzuba SA, Fedorova OS et al. Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway. Nucleic Acids Research. 2018 Nov 30;46(21):11454-11465. doi: 10.1093/nar/gky912

Author

Kuznetsova, Alexandra A. ; Matveeva, Anna G. ; Milov, Alexander D. et al. / Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway. In: Nucleic Acids Research. 2018 ; Vol. 46, No. 21. pp. 11454-11465.

BibTeX

@article{48244e6fd2bf4879a30c8e6d6d094f28,
title = "Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway",
abstract = "Human apurinic/apyrimidinic (AP) endonuclease APE1 catalyses the hydrolysis of phosphodiester bonds on the 5 side of an AP-site (in the base excision repair pathway) and of some damaged nucleotides (in the nucleotide incision repair pathway). The range of substrate specificity includes structurally unrelated damaged nucleotides. Here, to examine the mechanism of broad substrate specificity of APE1, we performed pulsed electron–electron double resonance (PELDOR) spectroscopy and pre-steady-state kinetic analysis with F{\"o}rster resonance energy transfer (FRET) detection of DNA conformational changes during DNA binding and lesion recognition. Equilibrium PELDOR and kinetic FRET data revealed that DNA binding by APE1 leads to noticeable damage-dependent bending of a DNA duplex. Molecular dynamics simulations showed that the damaged nucleotide is everted from the DNA helix and placed into the enzyme{\textquoteright}s binding pocket, which is formed by Asn-174, Asn-212, Asn-229, Ala-230, Phe-266 and Trp-280. Nevertheless, no damage-specific contacts were detected between these amino acid residues in the active site of the enzyme and model damaged substrates containing 1,N6-ethenoadenosine, -adenosine, 5,6-dihydrouridine or F-site. These data suggest that the substrate specificity of APE1 is controlled by the ability of a damaged nucleotide to flip out from the DNA duplex in response to an enzyme-induced DNA distortion.",
keywords = "Adenosine/analogs & derivatives, Catalytic Domain, Cloning, Molecular, DNA Damage, DNA Repair, DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry, DNA/chemistry, Electron Spin Resonance Spectroscopy, Escherichia coli/genetics, Fluorescence Resonance Energy Transfer, Gene Expression, Humans, Kinetics, Molecular Dynamics Simulation, Nucleic Acid Conformation, Oligodeoxyribonucleotides/chemistry, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Recombinant Proteins/chemistry, Substrate Specificity, Uridine/analogs & derivatives, ACTIVE-SITE, KINETIC MECHANISM, ABASIC SITE, CONFORMATIONAL DYNAMICS, DAMAGE RECOGNITION, STRUCTURAL-CHANGES, DIVALENT METAL-IONS, BASE-EXCISION, DNA-REPAIR, BINDING",
author = "Kuznetsova, {Alexandra A.} and Matveeva, {Anna G.} and Milov, {Alexander D.} and Vorobjev, {Yuri N.} and Dzuba, {Sergei A.} and Fedorova, {Olga S.} and Kuznetsov, {Nikita A.}",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2018.",
year = "2018",
month = nov,
day = "30",
doi = "10.1093/nar/gky912",
language = "English",
volume = "46",
pages = "11454--11465",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "21",

}

RIS

TY - JOUR

T1 - Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway

AU - Kuznetsova, Alexandra A.

AU - Matveeva, Anna G.

AU - Milov, Alexander D.

AU - Vorobjev, Yuri N.

AU - Dzuba, Sergei A.

AU - Fedorova, Olga S.

AU - Kuznetsov, Nikita A.

N1 - Publisher Copyright: © The Author(s) 2018.

PY - 2018/11/30

Y1 - 2018/11/30

N2 - Human apurinic/apyrimidinic (AP) endonuclease APE1 catalyses the hydrolysis of phosphodiester bonds on the 5 side of an AP-site (in the base excision repair pathway) and of some damaged nucleotides (in the nucleotide incision repair pathway). The range of substrate specificity includes structurally unrelated damaged nucleotides. Here, to examine the mechanism of broad substrate specificity of APE1, we performed pulsed electron–electron double resonance (PELDOR) spectroscopy and pre-steady-state kinetic analysis with Förster resonance energy transfer (FRET) detection of DNA conformational changes during DNA binding and lesion recognition. Equilibrium PELDOR and kinetic FRET data revealed that DNA binding by APE1 leads to noticeable damage-dependent bending of a DNA duplex. Molecular dynamics simulations showed that the damaged nucleotide is everted from the DNA helix and placed into the enzyme’s binding pocket, which is formed by Asn-174, Asn-212, Asn-229, Ala-230, Phe-266 and Trp-280. Nevertheless, no damage-specific contacts were detected between these amino acid residues in the active site of the enzyme and model damaged substrates containing 1,N6-ethenoadenosine, -adenosine, 5,6-dihydrouridine or F-site. These data suggest that the substrate specificity of APE1 is controlled by the ability of a damaged nucleotide to flip out from the DNA duplex in response to an enzyme-induced DNA distortion.

AB - Human apurinic/apyrimidinic (AP) endonuclease APE1 catalyses the hydrolysis of phosphodiester bonds on the 5 side of an AP-site (in the base excision repair pathway) and of some damaged nucleotides (in the nucleotide incision repair pathway). The range of substrate specificity includes structurally unrelated damaged nucleotides. Here, to examine the mechanism of broad substrate specificity of APE1, we performed pulsed electron–electron double resonance (PELDOR) spectroscopy and pre-steady-state kinetic analysis with Förster resonance energy transfer (FRET) detection of DNA conformational changes during DNA binding and lesion recognition. Equilibrium PELDOR and kinetic FRET data revealed that DNA binding by APE1 leads to noticeable damage-dependent bending of a DNA duplex. Molecular dynamics simulations showed that the damaged nucleotide is everted from the DNA helix and placed into the enzyme’s binding pocket, which is formed by Asn-174, Asn-212, Asn-229, Ala-230, Phe-266 and Trp-280. Nevertheless, no damage-specific contacts were detected between these amino acid residues in the active site of the enzyme and model damaged substrates containing 1,N6-ethenoadenosine, -adenosine, 5,6-dihydrouridine or F-site. These data suggest that the substrate specificity of APE1 is controlled by the ability of a damaged nucleotide to flip out from the DNA duplex in response to an enzyme-induced DNA distortion.

KW - Adenosine/analogs & derivatives

KW - Catalytic Domain

KW - Cloning, Molecular

KW - DNA Damage

KW - DNA Repair

KW - DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry

KW - DNA/chemistry

KW - Electron Spin Resonance Spectroscopy

KW - Escherichia coli/genetics

KW - Fluorescence Resonance Energy Transfer

KW - Gene Expression

KW - Humans

KW - Kinetics

KW - Molecular Dynamics Simulation

KW - Nucleic Acid Conformation

KW - Oligodeoxyribonucleotides/chemistry

KW - Protein Binding

KW - Protein Interaction Domains and Motifs

KW - Protein Structure, Secondary

KW - Recombinant Proteins/chemistry

KW - Substrate Specificity

KW - Uridine/analogs & derivatives

KW - ACTIVE-SITE

KW - KINETIC MECHANISM

KW - ABASIC SITE

KW - CONFORMATIONAL DYNAMICS

KW - DAMAGE RECOGNITION

KW - STRUCTURAL-CHANGES

KW - DIVALENT METAL-IONS

KW - BASE-EXCISION

KW - DNA-REPAIR

KW - BINDING

UR - http://www.scopus.com/inward/record.url?scp=85061134675&partnerID=8YFLogxK

U2 - 10.1093/nar/gky912

DO - 10.1093/nar/gky912

M3 - Article

C2 - 30329131

AN - SCOPUS:85061134675

VL - 46

SP - 11454

EP - 11465

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 21

ER -

ID: 18488633