G-quadruplex formation in human telomeric (TTAGGG)4 sequence with complementary strand in close vicinity under...

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Vertebrate chromosomes have telomeres with tandem (TTAGGG)n repeats.
• DNA replication creates a blunt leading strand and a G-rich overhang on the lagging strand telomere.
• G-rich overhangs can form G-quadruplex structures, but formation in double-stranded regions is unclear.

Purpose of the Study:

• To investigate G-quadruplex formation in double-stranded DNA mimicking in vivo telomere conditions.
• To determine if G-quadruplexes can form and dominate over duplex structures under competitive conditions.

Main Methods:

• Studied G-quadruplex formation in oligonucleotides and double-stranded DNA.
• Used molecular crowding conditions (e.g., PEG) to simulate in vivo environments.
• Analyzed competition between G-quadruplex and Watson-Crick duplex formation.

Main Results:

• In dilute solutions with K+, only duplex DNA was observed.
• Under molecular crowding, G-quadruplex formation preferentially dominated over duplex structures.
• Molecular crowding significantly stabilized G-quadruplexes and destabilized duplexes.

Conclusions:

• G-quadruplex structures can form at blunt telomere ends under molecular crowding.
• This formation competes with and can dominate over standard duplex structures.
• Suggests a potential alternative structural role for G-quadruplexes at telomere ends.