G-quartets assembly within a G-rich DNA flap. A possible event at the center of the HIV-1 genome

Nucleic Acids Res. 2002 Dec 1;30(23):5276-83. doi: 10.1093/nar/gkf644.


Stretches of guanines can associate in vitro through Hoogsteen hydrogen bonding to form four-stranded structures. In the HIV-1 central DNA flap, generated by reverse transcriptase at the end of retrotranscription, both the two 99 nt-long overlapping (+) strands contain two adjacent tracts of guanines. This study demonstrates that oligonucleotides containing these G-clusters form highly stable G-quadruplexes of various structures in vitro, whose formation was controlled by an easy and reversible protocol using sodium hydroxide. Among these sequences, a G'2 hairpin dimer was the most stable structure adopted by the 5'-tail of the (+) downstream strand. Since the two (+) strands of the HIV-1 central DNA flap hold these G-clusters, and based on the properties of reverse branch migration in DNA flaps, constructions using HIV-1 sequences were assembled to mimic small DNA flaps where the G-clusters are neighbors. G-quartets were successfully probed in such flaps. They were induced by potassium and by a dibenzophenanthroline derivative already known to stabilize them. Such results suggest some function(s) for G-quartets associated with a DNA flap in the HIV-1 pre-integration steps, and argue for their transient formation during the processing of G-rich DNA flaps at the time of replication and/or repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / biosynthesis*
  • DNA / chemistry
  • DNA / metabolism
  • DNA, Viral / chemistry*
  • DNA, Viral / metabolism
  • G-Quadruplexes
  • Genome, Viral
  • Guanine / chemistry*
  • HIV-1 / genetics*
  • Kinetics
  • Ligands
  • Models, Genetic
  • Motion
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides / chemistry
  • Phenanthrolines / pharmacology
  • Potassium / pharmacology
  • Repetitive Sequences, Nucleic Acid
  • Sodium Hydroxide


  • DNA, Viral
  • Ligands
  • Oligodeoxyribonucleotides
  • Phenanthrolines
  • Sodium Hydroxide
  • Guanine
  • DNA
  • Potassium