Interaction of human DNA topoisomerase I with G‐quartet structures

• Published in: Nucleic acids research Vol. 28; no. 24; pp. 4832 - 4838
• Main Authors: Arimondo, Paola B., Riou, Jean-François, Mergny, Jean-Louis, Tazi, Jamal, Sun, Jian-Sheng, Garestier, Thérèse, Hélène, Claude
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15.12.2000; Oxford Publishing Limited (England)
• Subjects: Base Sequence; Binding Sites; Biochemistry, Molecular Biology; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA Probes - chemistry; DNA Probes - genetics; DNA Probes - metabolism; DNA Topoisomerases, Type I - metabolism; DNA, Viral - chemistry; DNA, Viral - genetics; DNA, Viral - metabolism; DNA-Binding Proteins - metabolism; Guanine - chemistry; Guanine - metabolism; HIV-1 - genetics; Humans; Hydrogen Bonding; Life Sciences; Models, Molecular; Nucleic Acid Conformation; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - genetics; Oligodeoxyribonucleotides - metabolism; Protein Binding; telomere-binding-protein circular-dichroism complexes oligonucleotides d(cgg)(n) cleavage covalent g4-DNA form sgs1
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/28.24.4832

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.