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Nucleic Acids Research, 2000, Vol. 28, No. 24 4832-4838
© 2000 Oxford University Press

Interaction of human DNA topoisomerase I with G-quartet structures

Paola B. Arimondo, Jean-François Riou1, Jean-Louis Mergny*, Jamal Tazi2, Jian-Sheng Sun, Thérèse Garestier and Claude Hélène

Laboratoire de Biophysique, Muséum National d’Histoire Naturelle CNRS UMR 8646, INSERM U201, 43 rue Cuvier, 75231 Paris cedex 05, France, 1Aventis, Centre de Recherche de Vitry-Alfortville, 94403 Vitry-sur-Seine, France and 2Institut de Génétique Moléculaire de Montpellier CNRS UMR 5535, 1919 route de Mende, 34033 Montpellier, France

Because of their role in the control of the topological state of DNA, topoisomerases are ubiquitous and vital enzymes, which participate in nearly all events related to DNA metabolism including replication and transcription. We show here that human topoisomerase I (Topo I) plays an unexpected role of ‘molecular matchmaker’ for G-quartet formation. G-quadruplexes are multi-stranded structures held together by square planes of four guanines (‘G-quartets’) interacting by forming Hoogsteen hydrogen bonds. Topo I is able to promote the formation of four-stranded intermolecular DNA structures when added to single-stranded DNA containing a stretch of at least five guanines. We provide evidence that these complexes are parallel G-quartet structures, mediated by tetrads of hydrogen-bonded guanine. In addition, Topo I binds specifically to pre-formed parallel and anti-parallel G4–DNA.

* To whom correspondence should be addressed. Tel: +33 1 40 79 36 89; Fax: +33 1 40 79 37 05; Email: mergny{at}vnumail.comPresentaddress:PaolaB.Arimondo,INSERMU524andLaboratoiredePharmacologieAntitumoraleduCentreOscarLambret,IRCL,PlaceVerdun,59045Lille,France


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