Probing and regulating the activity of cellular enzymes by using DNA tetrahedron nanostructures

Given the essential role of apurinic/apyrimidinic endonuclease (APE1) in gene repair and cancer progression, we report a novel approach for probing and regulating cellular APE1 activity by using DNA tetrahedrons. The tetrahedron with an AP site-containing antenna exhibits high sensitivity and specif...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2019-06, Vol.1 (23), p.5959-5966
Main Authors: Zhang, Yi, Deng, Yingnan, Wang, Congshan, Li, Lidan, Xu, Lida, Yu, Yingjie, Su, Xin
Format: Article
Language:English
Subjects:
Cancer
Catalysis
Deoxyribonucleic acid
DNA
Enzymes
Fluorescence
Inhibitors
Nanostructure
Reagents
Regulators
Substrates
Tetrahedra
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Summary:Given the essential role of apurinic/apyrimidinic endonuclease (APE1) in gene repair and cancer progression, we report a novel approach for probing and regulating cellular APE1 activity by using DNA tetrahedrons. The tetrahedron with an AP site-containing antenna exhibits high sensitivity and specificity to APE1. It is suitable for APE1 in vitro detection (detection limit 5 pM) and cellular fluorescence imaging without any auxiliary transfection reagents, which discriminates the APE1 expression level of cancer cells and normal cells. In contrast, the tetrahedron with an AP site on its scaffold exhibits high binding affinity to APE1 but limits enzymatic catalysis making this nanostructure an APE1 inhibitor with an IC 50 of 14.8 nM. It suppresses the APE1 activity in living cells and sensitizes cancer cells to anticancer drugs. We also demonstrate that the APE1 probe and inhibitor can be switched allosterically via stand displacement, which holds potential for reversible inhibition of APE1. Our approach provides a new way for fabricating enzyme probes and regulators and new insights into enzyme-substrate interactions, and it can be expanded to regulate other nucleic acid related enzymes. Given the essential role of apurinic/apyrimidinic endonuclease (APE1) in gene repair and cancer progression, we report a novel approach for probing and regulating cellular APE1 activity by using DNA tetrahedrons.
ISSN:2041-6520
2041-6539
DOI:10.1039/c9sc01912j