Literature DB >> 10480928

Selective nucleosome disruption by drugs that bind in the minor groove of DNA.

D J Fitzgerald1, J N Anderson.   

Abstract

Previous studies have shown that drugs which bind in the DNA minor groove reduce the curvature of bent DNA. In this article, we examined the effects of these drugs on the nucleosome assembly of DNA molecules that display different degrees of intrinsic curvature. DAPI (4,6-diamidino-2-phenylindole) inhibited the assembly of a histone octamer onto a 192-base pair circular DNA fragment from Caenorhabditis elegans and destabilized a nucleosome that was previously assembled on this segment. The inhibitory effect was highly selective since it was not seen with nonbent molecules, bent molecules with noncircular shapes, or total genomic DNA. This marked template specificity was attributed to the binding of the ligand to multiple oligo A-tracts distributed over the length of the fragment. A likely mechanism for the effect is that the bound ligand prevents the further compression of the DNA into the minor groove which is required for assembly of DNA into nucleosomes. To further characterize the effects of the drug on chromatin formation, a nucleosome was assembled onto a 322-base pair DNA fragment that contained the circular element and a flanking nonbent segment of DNA. The position of the nucleosome along the fragment was then determined using a variety of nuclease probes including exonuclease III, micrococcal nuclease, DNase I, and restriction enzymes. The results of these studies revealed that the nucleosome was preferentially positioned along the circular element in the absence of DAPI but assembled onto the nonbent flanking sequence in the presence of the drug. DAPI also induced the directional movement of the nucleosome from the circular element onto the nonbent flanking sequence when a nucleosome preassembled onto this template was exposed to the drug under physiologically relevant conditions.

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Year:  1999        PMID: 10480928     DOI: 10.1074/jbc.274.38.27128

Source DB:  PubMed          Journal:  J Biol Chem        ISSN: 0021-9258            Impact factor:   5.157


  15 in total

1.  Exocyclic groups in the minor groove influence the backbone conformation of DNA.

Authors:  B Wellenzohn; W Flader; R H Winger; A Hallbrucker; E Mayer; K R Liedl
Journal:  Nucleic Acids Res       Date:  2001-12-15       Impact factor: 16.971

2.  Dicationic phenyl-2,2'-bichalcophenes and analogues as antiprotozoal agents.

Authors:  Mohamed A Ismail; Serry A El Bialy; Reto Brun; Tanja Wenzler; Rupesh Nanjunda; W David Wilson; David W Boykin
Journal:  Bioorg Med Chem       Date:  2010-12-05       Impact factor: 3.641

3.  Molecular mechanisms and kinetics between DNA and DNA binding ligands.

Authors:  Andy Sischka; Katja Toensing; Rainer Eckel; Sven David Wilking; Norbert Sewald; Robert Ros; Dario Anselmetti
Journal:  Biophys J       Date:  2004-10-29       Impact factor: 4.033

4.  Nuclear condensation and free radical scavenging: a dual mechanism of bisbenzimidazoles to modulate radiation damage to DNA.

Authors:  Urmila Tawar; Sandhya Bansal; Shiteshu Shrimal; Manish Singh; Vibha Tandon
Journal:  Mol Cell Biochem       Date:  2007-07-10       Impact factor: 3.396

5.  FACT maintains nucleosomes during transcription and stem cell viability in adult mice.

Authors:  Imon Goswami; Poorva Sandlesh; Aimee Stablewski; Ilya Toshkov; Alfiya F Safina; Mikhail Magnitov; Jianmin Wang; Katerina Gurova
Journal:  EMBO Rep       Date:  2022-02-18       Impact factor: 8.807

6.  Novel linear triaryl guanidines, N-substituted guanidines and potential prodrugs as antiprotozoal agents.

Authors:  Reem K Arafa; Mohamed A Ismail; Manoj Munde; W David Wilson; Tanja Wenzler; Reto Brun; David W Boykin
Journal:  Eur J Med Chem       Date:  2008-02-29       Impact factor: 6.514

7.  Oligonucleotide sequence motifs as nucleosome positioning signals.

Authors:  Clayton K Collings; Alfonso G Fernandez; Chad G Pitschka; Troy B Hawkins; John N Anderson
Journal:  PLoS One       Date:  2010-06-03       Impact factor: 3.240

8.  Synthesis and activity of azaterphenyl diamidines against Trypanosoma brucei rhodesiense and Plasmodium falciparum.

Authors:  Laixing Hu; Reem K Arafa; Mohamed A Ismail; Alpa Patel; Manoj Munde; W David Wilson; Tanja Wenzler; Reto Brun; David W Boykin
Journal:  Bioorg Med Chem       Date:  2009-08-07       Impact factor: 3.641

9.  Synthesis and SAR of alkanediamide-linked bisbenzamidines with anti-trypanosomal and anti-pneumocystis activity.

Authors:  Tien L Huang; Jean Jacques Vanden Eynde; Annie Mayence; Margaret S Collins; Melanie T Cushion; Donna Rattendi; Indira Londono; Lakshman Mazumder; Cyrus J Bacchi; Nigel Yarlett
Journal:  Bioorg Med Chem Lett       Date:  2009-08-23       Impact factor: 2.823

10.  BENA435, a new cell-permeant photoactivated green fluorescent DNA probe.

Authors:  Alexandra Erve; Yasmina Saoudi; Sylvie Thirot; Corinne Guetta-Landras; Jean-Claude Florent; Chi-Hung Nguyen; David S Grierson; Andrei V Popov
Journal:  Nucleic Acids Res       Date:  2006-03-17       Impact factor: 16.971

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