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Papers In Press, published online ahead of print December 26, 2001
Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Corresponding Author: marchanc{at}mail.nih.gov
Human nuclear DNA topoisomerase I (top1) plays a crucial role in DNA replication, transcription and chromosome condensation. In this study, we show that intra- and inter-molecular guanosine-quartets (G-quartets) can inhibit top1-mediated DNA cleavage at a high affinity site. Top1-mediated DNA cleavage was also inhibited by a 16-mer single-stranded oligodeoxynucleotide (ODN) containing a G-rich sequence (G2T2G5TG2TG3) and by its RNA equivalent, which do not form G-quartet structures. Comparison of various single-stranded ODN for their ability to inhibit top1-mediated DNA cleavage indicated that G-rich sequences containing repeats of 2 or 3 consecutive guanines interspaced with thymines specifically inhibited top1. We also found that both single-stranded and G-quartet-forming ODNs bind to top1 without being cleaved by the enzyme. These results demonstrate that either DNA or RNA G-rich single-stranded and G-quartet-forming oligonucleotides can bind to top1 and prevent cleavage of duplex DNA.
J. Biol. Chem, 10.1074/jbc.M106372200
Submitted on July 9, 2001
Revised on November 5, 2001
Accepted on December 25, 2001
Interaction of human nuclear topoisomerase I with guanosine-quartet-forming and guanosine-rich single-stranded DNA and RNA oligonucleotides
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