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Solution Structure of a MYC Promoter G-Quadruplex with 1:6:1 Loop Length
Jonathan Dickerhoff1, Buket Onel1, Luying Chen1
1College of Pharmacy, Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 W Stadium Avenue, West Lafayette, Indiana 47907, United States.
ACS Omega
|March 8, 2019
Summary
The MYC oncogene
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- The MYC oncogene is frequently deregulated in cancers.
- G-quadruplex (G4) DNA structures in the MYC promoter can suppress transcription.
- G4s are potential therapeutic targets in cancer treatment.
Purpose of the Study:
- To investigate the structural basis of MYC G-quadruplex polymorphism.
- To understand the interaction between Nucleolin and the 1:6:1 MYC G4 conformer.
- To provide structural insights for targeted drug design.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to determine solution structures.
- Analysis of G-quadruplex folding conformers (1:2:1 and 1:6:1).
- Investigation of protein-G4 interactions using Nucleolin.
Main Results:
- The 1:6:1 MYC G4 conformer exhibits a distinct 5'-capping structure compared to the 1:2:1 form.
- The 6-nucleotide central loop is crucial for the 1:6:1 conformer's unique structure.
- Nucleolin preferentially binds to the 1:6:1 MYC G4 conformer.
Conclusions:
- MYC G-quadruplex structures are polymorphic, with distinct loop and capping features.
- The 1:6:1 conformer's specific structure is recognized by Nucleolin, suggesting physiological relevance.
- Structural data facilitates understanding of G4-protein interactions and development of selective therapeutics.
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