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A Hybrid G‑Quadruplex Structure Formed by a Sequence from the MAX Gene.

Xiaodong Hu1, Xiao Ni1, Wenxian Lan2

  • 1State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.

JACS Au
|November 28, 2025
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Summary

Researchers determined the NMR solution structure of a unique G-quadruplex (G4) DNA from the MAX gene. This G4 is stable under physiological conditions and may be a target for cancer therapy.

Keywords:
G-quadruplexMAXNMR spectroscopyhybridpolarity

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Area of Science:

  • Structural Biology
  • Genetics
  • Biochemistry

Background:

  • The MAX gene encodes a transcription factor that partners with the oncoprotein MYC.
  • G-quadruplexes (G4s) are non-canonical DNA structures implicated in various biological processes.
  • Understanding G4 structures is crucial for developing targeted therapies.

Purpose of the Study:

  • To elucidate the NMR solution structure of a specific G-quadruplex (G4) DNA sequence from the MAX gene.
  • To characterize the unique topology and stability of this MAX G4 structure.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the solution structure.
  • Analysis of DNA sequence d-[AG3AG4A2G4TGA2G4A] from the MAX gene's first intron.

Main Results:

  • A unimolecular G4 with a [3 + 1] hybrid topology was identified, featuring propeller, diagonal, and lateral loops.
  • The G4 exhibits a stable structure under physiological conditions, even without annealing.
  • Unusual features include a G·(A-G) triad in the diagonal loop and a T·G base pair in the lateral loop.
  • The MAX G4 acts as a barrier to DNA polymerase.

Conclusions:

  • This study reports the first example of this unique G4 topology with unmodified nucleotides.
  • The findings offer insights into G4 folding and highlight the MAX G4 as a potential therapeutic target.
  • The stability and polymerase barrier properties suggest a role in gene regulation.