A new pathway of DNA G-quadruplex formation

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• G-quadruplexes are crucial nucleic acid structures involved in various biological processes.
• Understanding G-quadruplex folding pathways is essential for comprehending their function and regulation.

Purpose of the Study:

• To characterize a newly identified folding intermediate of the Oxytricha nova telomeric Oxy-1.5 G-quadruplex.
• To elucidate the folding pathway and kinetics of Oxy-1.5 G-quadruplex formation.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy
• Native gel electrophoresis
• Circular Dichroism (CD) spectroscopy
• Thermal Differential Spectra (TDS)
• Differential Scanning Calorimetry (DSC)

Main Results:

• A novel folding intermediate (i-Oxy-1.5) was characterized in aqueous solution.
• The intermediate exists in two symmetric bimolecular forms with specific guanine base pairing.
• Folding from the intermediate to the G-quadruplex is significantly faster than from single strands, involving fewer intermediates.

Conclusions:

• A new folding pathway for the Oxy-1.5 G-quadruplex is proposed.
• G-rich DNA sequences can form pre-organized structures that facilitate rapid G-quadruplex folding upon cation interaction.