Polyamines preferentially interact with bent adenine tracts in double-stranded DNA

Lindemose, Søren; Nielsen, Peter E.; Møllegaard, Niels Erik

doi:10.1093/nar/gki319

Cited by 49 publications

(33 citation statements)

References 56 publications

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“…Natural polyamines bind to the DNA 47 . Polyamines like spermidine and spermine are also known to promote growth 48 or influence gene expression 49 .…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Broad-Complex Gene Expression of Bombyx mori by Oligopyrrole Carboxamides Enhances Silk Production

Ali

Bovilla

Mysarla

et al. 2017

Sci Rep

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Bombyx mori (B. mori) is important due to its major role in the silk production. Though DNA binding ligands often influence gene expression, no attempt has been made to exploit their use in sericulture. The telomeric heterochromatin of B. mori is enriched with 5′-TTAGG-3′ sequences. These sequences were also found to be present in several genes in the euchromatic regions. We examined three synthetic oligopyrrole carboxamides that target 5′-TTAGG-3′ sequences in controlling the gene expression in B. mori. The ligands did not show any defect or feeding difference in the larval stage, crucial for silk production. The ligands caused silencing of various isoforms of the broad-complex transcription factor and cuticle proteins which resulted in late pupal developmental defects. Furthermore, treatment with such drugs resulted in statistically enhanced cocoon weight, shell weight, and silk yield. This study shows for the first time use of oligopyrrole carboxamide drugs in controlling gene expression in B. mori and their long term use in enhancing silk production.

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“…Natural polyamines bind to the DNA 47 . Polyamines like spermidine and spermine are also known to promote growth 48 or influence gene expression 49 .…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Broad-Complex Gene Expression of Bombyx mori by Oligopyrrole Carboxamides Enhances Silk Production

Ali

Bovilla

Mysarla

et al. 2017

Sci Rep

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“…In addition to the vectorization via the PTS, the spermine moiety of F14512 can be exploited for the high affinity of polyammonium cation for DNA (47). This property has already been used to strengthen the activity of several DNA-damaging agents, including topoisomerase II poisons (20,48).…”

Section: Discussionmentioning

confidence: 99%

F14512, a Potent Antitumor Agent Targeting Topoisomerase II Vectored into Cancer Cells via the Polyamine Transport System

Barret¹,

Kruczynski²,

Vispé³

et al. 2008

Cancer Research

139

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The polyamine transport system (PTS) is an energy-dependent machinery frequently overactivated in cancer cells with a high demand for polyamines. We have exploited the PTS to selectively deliver a polyamine-containing drug to cancer cells. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. The polyamine tail supports three complementary functions: (a) facilitate formulation of a watersoluble compound, (b) increase DNA binding to reinforce topoisomerase II inhibition, and (c) facilitate selective uptake by tumor cells via the PTS. F14512 is 73-fold more cytotoxic to Chinese hamster ovary cells compared with CHO-MG cells with a reduced PTS activity. A decreased sensitivity of L1210 leukemia cells to F14512 was observed in the presence of putrescine, spermidine, and spermine. In parallel, the spermine moiety considerably enhances the drug-DNA interaction, leading to a reinforced inhibition of topoisomerase II. The spermine tail of F14512 serves as a cell delivery vehicle as well as a DNA anchor, and this property translates at the cellular level into a distinct pharmacologic profile. Twentynine human solid or hematologic cell lines were used to characterize the high cytotoxic potential of F14512 (median IC 50 of 0.18 Mmol/L). Finally, the potent antitumor activity of F14512 in vivo was evidenced with a MX1 human breast tumor xenograft model, with partial and complete tumor regressions. This work supports the clinical development of F14512 as a novel targeted cytotoxic drug and sheds light on the concept of selective delivery of drugs to tumor cells expressing the PTS. [Cancer Res 2008;68(23):9845-53]

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“…Open bold letters represent nucleotides whose phosphate groups were judged as likely to be protected by residues in the loops/termini missing in the crystal structure, on the basis of their approximate spatial orientation. and up to 200 ng ANAC019 per sample [32][33][34]. In brief, the purified [ 32 P]-labelled DNA fragments were subjected to either DNase I or uranyl photo-cleavage in binding buffer (see [13]).…”

Section: Uranyl Photo-cleavage Analysis and Dnase I Footprintingmentioning

confidence: 99%

“…Uranyl photo-cleavage can be used to study phosphate contacts involved in protein-and ligand-DNA complexes [32,33]. The technique exploits the fact that the uranyl-(VI) cation (UO 2 2 + ) forms strong complexes with accessible phosphates of the DNA backbone and upon irradiation is excited, which initiates a complex photo-oxidation process eventually leading to strand break.…”

Section: Dnase I Footprinting and Uranyl Photo-cleavage Analysis Of Amentioning

confidence: 99%

DNA binding by the plant-specific NAC transcription factors in crystal and solution: a firm link to WRKY and GCM transcription factors

Welner

Lindemose

Grossmann

et al. 2012

Biochemical Journal

100

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NAC (NAM/ATAF/CUC) plant transcription factors regulate essential processes in development, stress responses and nutrient distribution in important crop and model plants (rice, Populus, Arabidopsis), which makes them highly relevant in the context of crop optimization and bioenergy production. The structure of the DNA-binding NAC domain of ANAC019 has previously been determined by X-ray crystallography, revealing a dimeric and predominantly β-fold structure, but the mode of binding to cognate DNA has remained elusive. In the present study, information from low resolution X-ray structures and small angle X-ray scattering on complexes with oligonucleotides, mutagenesis and (DNase I and uranyl photo-) footprinting, is combined to form a structural view of DNA-binding, and for the first time provide experimental evidence for the speculated relationship between plant-specific NAC proteins, WRKY transcription factors and the mammalian GCM (Glial cell missing) transcription factors, which all use a β-strand motif for DNA-binding. The structure shows that the NAC domain inserts the edge of its core β-sheet into the major groove, while leaving the DNA largely undistorted. The structure of the NAC-DNA complex and a new crystal form of the unbound NAC also indicate limited flexibility of the NAC dimer arrangement, which could be important in recognizing suboptimal binding sites.

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Polyamines preferentially interact with bent adenine tracts in double-stranded DNA

Cited by 49 publications

References 56 publications

Knockdown of Broad-Complex Gene Expression of Bombyx mori by Oligopyrrole Carboxamides Enhances Silk Production

Knockdown of Broad-Complex Gene Expression of Bombyx mori by Oligopyrrole Carboxamides Enhances Silk Production

F14512, a Potent Antitumor Agent Targeting Topoisomerase II Vectored into Cancer Cells via the Polyamine Transport System

DNA binding by the plant-specific NAC transcription factors in crystal and solution: a firm link to WRKY and GCM transcription factors

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