Interaction of human nuclear topoisomerase I with guanosine quartet-forming and guanosine-rich single-stranded DNA and RNA oligonucleotides.
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 intermolecular 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 (G(2)T(2)G(5)TG(2)TG(3)) and by its RNA equivalent, neither of which form G-quartet structures. A 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.
Marchand
Christophe
C
Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Pourquier
Philippe
P
Laco
Gary S
GS
Jing
Naijie
N
Pommier
Yves
Y
D001483:Base Sequence; D002166:Camptothecin / Q000494:pharmacology; D002467:Cell Nucleus / Q000201:enzymology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism*; D006151:Guanosine / Q000737:chemistry*; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D009843:Oligoribonucleotides / Q000378:metabolism*
D004277:DNA, Single-Stranded; D009838:Oligodeoxyribonucleotides; D009843:Oligoribonucleotides; D006151:Guanosine; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin