Propeller-type parallel-stranded G-quadruplexes in the human c-myc promoter

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• The nuclease-hypersensitivity element III1 in the c-myc promoter is crucial for transcriptional activation of the c-myc oncogene.
• This element is a potential anticancer target due to its role in regulating c-myc expression.
• Previous studies proposed antiparallel G-quadruplex structures (basket and chair forms) for the guanine-rich strand.

Purpose of the Study:

• To investigate the structural conformation of specific G-rich sequences from the c-myc nuclease-hypersensitivity element III1.
• To determine whether these sequences form parallel-stranded G-quadruplex structures.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to analyze the structures.
• Two specific G-rich sequences were synthesized and studied in a potassium (K+)-containing solution.

Main Results:

• The study revealed that the two G-rich sequences form intramolecular propeller-type parallel-stranded G-quadruplexes.
• These structures feature a core of three stacked G-tetrads formed by four parallel G-stretches with anti guanines.
• Three double-chain-reversal loops connect the G-tetrad layers, with loop lengths of one, two, or six residues.

Conclusions:

• The findings demonstrate the formation of parallel-stranded G-quadruplexes by specific c-myc promoter sequences.
• These parallel structures differ from previously proposed antiparallel models.
• The structural characterization provides insights into G-quadruplex formation in a biologically relevant promoter region.