A DNA polymerase stop assay for G-quadruplex-interactive compounds

Nucleic Acids Res. 1999 Jan 15;27(2):537-42. doi: 10.1093/nar/27.2.537.

Abstract

We have developed and characterized an assay for G-quadruplex-interactive compounds that makes use of the fact that G-rich DNA templates present obstacles to DNA synthesis by DNA polymerases. Using Taq DNA polymerase and the G-quadruplex binding 2, 6-diamidoanthraquinone BSU-1051, we find that BSU-1051 leads to enhanced arrest of DNA synthesis in the presence of K+by stabilizing an intramolecular G-quadruplex structure formed by four repeats of either TTGGGG or TTAGGG in the template strand. The data provide additional evidence that BSU-1051 modulates telomerase activity by stabilization of telomeric G-quadruplex DNA and point to a polymerase arrest assay as a sensitive method for screening for G-quadruplex-interactive agents with potential clinical utility.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anthraquinones / pharmacology*
  • Cations, Monovalent / pharmacology
  • DNA / biosynthesis*
  • G-Quadruplexes
  • Guanine Nucleotides / metabolism*
  • Nucleic Acid Conformation
  • Potassium / pharmacology
  • Taq Polymerase / metabolism*
  • Telomerase / drug effects*

Substances

  • Anthraquinones
  • BSU 1051
  • Cations, Monovalent
  • Guanine Nucleotides
  • DNA
  • Taq Polymerase
  • Telomerase
  • Potassium