Interaction of human DNA topoisomerase I with G-quartet structures

Because of their role in the control of the topological state of DNA, topoi somerases 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 o f 'molecular matchmaker' for G-quartet formation, G-quadruplexes are multi- stranded structures held together by square planes of four guanines ('G-qua rtets') interacting by forming Hoogsteen hydrogen bonds. Topo I is able to promote the formation of four-stranded intermolecular DNA structures when a dded 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.