Inhibition of unwinding of G-quadruplex structures by Sgs1 helicase in the presence of N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide, a G-quadruplex-interactive ligand

H. Han, R. J. Bennett, Laurence Hurley

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide (PIPER), a perylene derivative, is a very potent and selective G-quadruplex DNA-interactive agent. It has been shown to inhibit DNA polymerase and telomerase by stacking externally to the G-tetrads in the G-quadruplex structures. Recently, we have demonstrated that this small molecule greatly accelerates the assembly of G-quadruplex structures in a cell-free system. In this report, we present data demonstrating that PIPER prevents the unwinding of G-quadruplex structures by yeast Sgsl helicase. Sgsl belongs to the RecQ DNA helicase family whose members include other G-quadruplex DNA unwinding helicases, such as human Bloom's syndrome and human Werner's syndrome helicases. PIPER specifically prevents the unwinding of G-quadruplex DNA but not duplex DNA by Sgsl. Competition experiments indicate that this inhibitory activity is due to the interaction of PIPER with G-quadruplex structures rather than the helicase itself. These results combined with previous studies suggest a possible mechanism of action for these G-quadruplex-interactive agents inside cells: they might induce G-quadruplex formation in G-rich regions on genomic DNA, stabilize these structures, and prevent them from being cleared by enzymes such as helicases. The G-quadruplex structures may, in turn, disrupt some critical cellular events such as DNA replication, transcription regulation, and telomere maintenance.

Original languageEnglish (US)
Pages (from-to)9311-9316
Number of pages6
JournalBiochemistry
Volume39
Issue number31
DOIs
StatePublished - Aug 8 2000

Fingerprint

G-Quadruplexes
Ligands
DNA
DNA Helicases
RecQ Helicases
Perylene
Telomerase
DNA-Directed DNA Polymerase
Transcription
Yeast
Bloom Syndrome
perylenetetracarboxylic diimide
Inhibition (Psychology)
Cell-Free System
Derivatives
Telomere
Molecules
DNA Replication
Enzymes
Yeasts

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{31d5db2673e242b498a63cbce3fc5544,
title = "Inhibition of unwinding of G-quadruplex structures by Sgs1 helicase in the presence of N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide, a G-quadruplex-interactive ligand",
abstract = "N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide (PIPER), a perylene derivative, is a very potent and selective G-quadruplex DNA-interactive agent. It has been shown to inhibit DNA polymerase and telomerase by stacking externally to the G-tetrads in the G-quadruplex structures. Recently, we have demonstrated that this small molecule greatly accelerates the assembly of G-quadruplex structures in a cell-free system. In this report, we present data demonstrating that PIPER prevents the unwinding of G-quadruplex structures by yeast Sgsl helicase. Sgsl belongs to the RecQ DNA helicase family whose members include other G-quadruplex DNA unwinding helicases, such as human Bloom's syndrome and human Werner's syndrome helicases. PIPER specifically prevents the unwinding of G-quadruplex DNA but not duplex DNA by Sgsl. Competition experiments indicate that this inhibitory activity is due to the interaction of PIPER with G-quadruplex structures rather than the helicase itself. These results combined with previous studies suggest a possible mechanism of action for these G-quadruplex-interactive agents inside cells: they might induce G-quadruplex formation in G-rich regions on genomic DNA, stabilize these structures, and prevent them from being cleared by enzymes such as helicases. The G-quadruplex structures may, in turn, disrupt some critical cellular events such as DNA replication, transcription regulation, and telomere maintenance.",
author = "H. Han and Bennett, {R. J.} and Laurence Hurley",
year = "2000",
month = "8",
day = "8",
doi = "10.1021/bi000482r",
language = "English (US)",
volume = "39",
pages = "9311--9316",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "31",

}

TY - JOUR

T1 - Inhibition of unwinding of G-quadruplex structures by Sgs1 helicase in the presence of N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide, a G-quadruplex-interactive ligand

AU - Han, H.

AU - Bennett, R. J.

AU - Hurley, Laurence

PY - 2000/8/8

Y1 - 2000/8/8

N2 - N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide (PIPER), a perylene derivative, is a very potent and selective G-quadruplex DNA-interactive agent. It has been shown to inhibit DNA polymerase and telomerase by stacking externally to the G-tetrads in the G-quadruplex structures. Recently, we have demonstrated that this small molecule greatly accelerates the assembly of G-quadruplex structures in a cell-free system. In this report, we present data demonstrating that PIPER prevents the unwinding of G-quadruplex structures by yeast Sgsl helicase. Sgsl belongs to the RecQ DNA helicase family whose members include other G-quadruplex DNA unwinding helicases, such as human Bloom's syndrome and human Werner's syndrome helicases. PIPER specifically prevents the unwinding of G-quadruplex DNA but not duplex DNA by Sgsl. Competition experiments indicate that this inhibitory activity is due to the interaction of PIPER with G-quadruplex structures rather than the helicase itself. These results combined with previous studies suggest a possible mechanism of action for these G-quadruplex-interactive agents inside cells: they might induce G-quadruplex formation in G-rich regions on genomic DNA, stabilize these structures, and prevent them from being cleared by enzymes such as helicases. The G-quadruplex structures may, in turn, disrupt some critical cellular events such as DNA replication, transcription regulation, and telomere maintenance.

AB - N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide (PIPER), a perylene derivative, is a very potent and selective G-quadruplex DNA-interactive agent. It has been shown to inhibit DNA polymerase and telomerase by stacking externally to the G-tetrads in the G-quadruplex structures. Recently, we have demonstrated that this small molecule greatly accelerates the assembly of G-quadruplex structures in a cell-free system. In this report, we present data demonstrating that PIPER prevents the unwinding of G-quadruplex structures by yeast Sgsl helicase. Sgsl belongs to the RecQ DNA helicase family whose members include other G-quadruplex DNA unwinding helicases, such as human Bloom's syndrome and human Werner's syndrome helicases. PIPER specifically prevents the unwinding of G-quadruplex DNA but not duplex DNA by Sgsl. Competition experiments indicate that this inhibitory activity is due to the interaction of PIPER with G-quadruplex structures rather than the helicase itself. These results combined with previous studies suggest a possible mechanism of action for these G-quadruplex-interactive agents inside cells: they might induce G-quadruplex formation in G-rich regions on genomic DNA, stabilize these structures, and prevent them from being cleared by enzymes such as helicases. The G-quadruplex structures may, in turn, disrupt some critical cellular events such as DNA replication, transcription regulation, and telomere maintenance.

UR - http://www.scopus.com/inward/record.url?scp=0034622547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034622547&partnerID=8YFLogxK

U2 - 10.1021/bi000482r

DO - 10.1021/bi000482r

M3 - Article

C2 - 10924124

AN - SCOPUS:0034622547

VL - 39

SP - 9311

EP - 9316

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 31

ER -