The Effect of DNA Sequence Directionality on G-Quadruplex Folding

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• G-rich DNA sequences can form G-quadruplex structures.
• The topology and stability of G-quadruplexes are influenced by various factors, including sequence and ions.
• Understanding G-quadruplex polymorphism is crucial for their potential physiological roles.

Purpose of the Study:

• To investigate the effect of sequence inversion on G-quadruplex formation and structure.
• To determine how ion presence (K+ vs. Na+) influences G-quadruplex folding.
• To explore the role of primary DNA sequence in G-quadruplex structural diversity.

Main Methods:

• Circular Dichroism (CD) spectroscopy
• UV spectroscopy
• Nuclear Magnetic Resonance (NMR) spectroscopy

Main Results:

• Sequence inversion (5'→3' vs. 3'→5') substantially affects the number of G-quadruplex structures formed.
• The type of G-quadruplex fold is determined by the presence of K+ or Na+ ions.
• Oligonucleotides in the 5'→3' direction exhibit higher melting temperatures than their 3'→5' counterparts in both KCl and NaCl.
• Primary sequence is critical for the structural diversity of G-quadruplexes.

Conclusions:

• Sequence reversal in G-rich DNA significantly impacts G-quadruplex polymorphism.
• The findings provide insights for predicting G-quadruplex topology based on sequence and ion conditions.
• This study enhances the understanding of G-quadruplex structural diversity and potential biological functions.