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

Haiyong Han; Laurence H. Hurley; Miguel Salazar

doi:10.1093/nar/27.2.537

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

Haiyong Han, Laurence H. Hurley, Miguel Salazar

Research output: Contribution to journal › Article › peer-review

228 Scopus citations

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.

Original language	English (US)
Pages (from-to)	537-542
Number of pages	6
Journal	Nucleic acids research
Volume	27
Issue number	2
DOIs	https://doi.org/10.1093/nar/27.2.537
State	Published - Jan 15 1999
Externally published	Yes

ASJC Scopus subject areas

Genetics

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title = "A DNA polymerase stop assay for G-quadruplex-interactive compounds",

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.",

author = "Haiyong Han and Hurley, {Laurence H.} and Miguel Salazar",

note = "Funding Information: We thank Dr Stephen Neidle for providing the BSU-1051. We also thank other members of the NCDDG for helpful discussions and David Bishop for proofreading, editing and preparing the final version of the manuscript. This research was supported by grants from the National Institutes of Health (CA49751 to L.H. and CA77000 to M.S.) and a National Cooperative Drug Discovery Group grant (NCDDG, CA67760) from the National Cancer Institute.",

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T1 - A DNA polymerase stop assay for G-quadruplex-interactive compounds

AU - Han, Haiyong

AU - Hurley, Laurence H.

AU - Salazar, Miguel

N1 - Funding Information: We thank Dr Stephen Neidle for providing the BSU-1051. We also thank other members of the NCDDG for helpful discussions and David Bishop for proofreading, editing and preparing the final version of the manuscript. This research was supported by grants from the National Institutes of Health (CA49751 to L.H. and CA77000 to M.S.) and a National Cooperative Drug Discovery Group grant (NCDDG, CA67760) from the National Cancer Institute.

PY - 1999/1/15

Y1 - 1999/1/15

N2 - 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.

AB - 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.

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

Abstract

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