Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Mechanism of stimulation of DNA binding of the transcription factors by human apurinic/apyrimidinic endonuclease 1, APE1. / Bazlekowa-Karaban, Milena; Prorok, Paulina; Baconnais, Sonia и др.
в: DNA Repair, Том 82, 102698, 01.10.2019, стр. 102698.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Mechanism of stimulation of DNA binding of the transcription factors by human apurinic/apyrimidinic endonuclease 1, APE1
AU - Bazlekowa-Karaban, Milena
AU - Prorok, Paulina
AU - Baconnais, Sonia
AU - Taipakova, Sabira
AU - Akishev, Zhiger
AU - Zembrzuska, Dominika
AU - Popov, Alexander V.
AU - Endutkin, Anton V.
AU - Groisman, Regina
AU - Ishchenko, Alexander A.
AU - Matkarimov, Bakhyt T.
AU - Bissenbaev, Amangeldy
AU - Le Cam, Eric
AU - Zharkov, Dmitry O.
AU - Tudek, Barbara
AU - Saparbaev, Murat
N1 - Publisher Copyright: © 2019 Elsevier B.V.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Aerobic respiration generates reactive oxygen species (ROS), which can damage nucleic acids, proteins and lipids. A number of transcription factors (TFs) contain redox-sensitive cysteine residues at their DNA-binding sites, hence ROS-induced thiol oxidation strongly inhibits their recognition of the cognate DNA sequences. Major human apurinic/apyrimidinic (AP) endonuclease 1 (APE1/APEX1/HAP-1), referred also as a redox factor 1 (Ref-1), stimulates the DNA binding activities of the oxidized TFs such as AP-1 and NF-κB. Also, APE1 participates in the base excision repair (BER) and nucleotide incision repair (NIR) pathways to remove oxidative DNA base damage. At present, the molecular mechanism underlying the TF-stimulating/redox function of APE1 and its biological role remains disputed. Here, we provide evidence that, instead of direct cysteine reduction in TFs by APE1, APE1-catalyzed NIR and TF-stimulating activities may be based on transient cooperative binding of APE1 to DNA and induction of conformational changes in the helix. The structure of DNA duplex strongly influences NIR and TF-stimulating activities. Homologous plant AP endonucleases lacking conserved cysteine residues stimulate DNA binding of the p50 subunit of NF-κB. APE1 acts synergistically with low-molecular-weight reducing agents on TFs. Finally, APE1 stimulates DNA binding of the redox-insensitive p50-C62S mutant protein. Electron microscopy imaging of APE1 complexes with DNA revealed preferential polymerization of APE1 on the gapped and intrinsically curved DNA duplexes. Molecular modeling offers a structural explanation how full-length APE1 can oligomerize on DNA. In conclusion, we propose that DNA-directed APE1 oligomerization can be regarded as a substitute for diffusion of APE1 along the DNA contour to probe for anisotropic flexibility. APE1 oligomers exacerbate pre-existing distortions in DNA and enable both NIR activity and DNA binding by TFs regardless of their oxidation state.
AB - Aerobic respiration generates reactive oxygen species (ROS), which can damage nucleic acids, proteins and lipids. A number of transcription factors (TFs) contain redox-sensitive cysteine residues at their DNA-binding sites, hence ROS-induced thiol oxidation strongly inhibits their recognition of the cognate DNA sequences. Major human apurinic/apyrimidinic (AP) endonuclease 1 (APE1/APEX1/HAP-1), referred also as a redox factor 1 (Ref-1), stimulates the DNA binding activities of the oxidized TFs such as AP-1 and NF-κB. Also, APE1 participates in the base excision repair (BER) and nucleotide incision repair (NIR) pathways to remove oxidative DNA base damage. At present, the molecular mechanism underlying the TF-stimulating/redox function of APE1 and its biological role remains disputed. Here, we provide evidence that, instead of direct cysteine reduction in TFs by APE1, APE1-catalyzed NIR and TF-stimulating activities may be based on transient cooperative binding of APE1 to DNA and induction of conformational changes in the helix. The structure of DNA duplex strongly influences NIR and TF-stimulating activities. Homologous plant AP endonucleases lacking conserved cysteine residues stimulate DNA binding of the p50 subunit of NF-κB. APE1 acts synergistically with low-molecular-weight reducing agents on TFs. Finally, APE1 stimulates DNA binding of the redox-insensitive p50-C62S mutant protein. Electron microscopy imaging of APE1 complexes with DNA revealed preferential polymerization of APE1 on the gapped and intrinsically curved DNA duplexes. Molecular modeling offers a structural explanation how full-length APE1 can oligomerize on DNA. In conclusion, we propose that DNA-directed APE1 oligomerization can be regarded as a substitute for diffusion of APE1 along the DNA contour to probe for anisotropic flexibility. APE1 oligomers exacerbate pre-existing distortions in DNA and enable both NIR activity and DNA binding by TFs regardless of their oxidation state.
KW - AP endonuclease
KW - Base excision repair
KW - Nucleotide incision repair
KW - Oxidative damage
KW - Redox regulation
KW - Transcription factors
KW - TERMINAL DOMAIN
KW - BASE EXCISION
KW - P50 SUBUNIT
KW - APURINIC ENDONUCLEASE
KW - LYSINE RESIDUES
KW - REDOX REGULATION
KW - GENE-EXPRESSION
KW - ANISOTROPIC NETWORK MODEL
KW - NF-KAPPA-B
KW - WEB SERVER
UR - http://www.scopus.com/inward/record.url?scp=85071902129&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2019.102698
DO - 10.1016/j.dnarep.2019.102698
M3 - Article
C2 - 31518879
AN - SCOPUS:85071902129
VL - 82
SP - 102698
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
M1 - 102698
ER -
ID: 21467500