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

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 guanine...

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Bibliographic Details
Published in:Nucleic acids research 2002-12, Vol.30 (23), p.5276-5283
Main Authors: Lyonnais, Sébastien, Hounsou, Candide, Teulade‐Fichou, Marie‐Paule, Jeusset, Josette, Cam, Eric Le, Mirambeau, Gilles
Format: Article
Language:English
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Summary: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.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkf644