An antiparallel G-quadruplex structure with a 5'-end overhang forms predominantly at the human telomeric ds-ss DNA...

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Human telomeric sequences form G-quadruplex structures crucial for telomere stability.
• Existing structural studies primarily focus on G-quadruplexes with uninterrupted G-tracts.
• The impact of interrupted G-tracts on G-quadruplex conformation is largely unknown.

Purpose of the Study:

• To investigate the structural consequences of a split G-tract in human telomeric sequences.
• To determine the three-dimensional structure of a human telomeric G-quadruplex with a modified G-tract.
• To explore the formation preferences of this modified G-quadruplex in biologically relevant contexts.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to determine the solution structure.
• Analysis of sequence variations and their impact on G-quadruplex folding.
• Investigating formation at double-strand/single-strand DNA junctions.

Main Results:

• The human telomeric sequence with a split G-tract adopts an antiparallel G-quadruplex topology.
• A disordered GTT segment was observed at the 5'-end of the structure.
• This specific conformation is preferentially formed at DNA junctions.

Conclusions:

• The structural diversity of human telomeric G-quadruplexes is greater than previously appreciated.
• Split G-tracts can lead to distinct G-quadruplex conformations.
• Understanding these structures is vital for telomere biology and potential therapeutic targeting.