Elevated polyamines induce c-MYC overexpression by perturbing quadruplex-WC duplex equilibrium. Kumar, N., Basundra, R., & Maiti, S. Nucleic acids research, 37(10):3321–31, June, 2009. ![Elevated polyamines induce c-MYC overexpression by perturbing quadruplex-WC duplex equilibrium. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex The biological role of quadruplexes and polyamines has been independently associated with cancer. However, quadruplex-polyamine mediated transcriptional regulation remain unaddressed. Herein, using c-MYC quadruplex model, we have attempted to understand quadruplex-polyamine interaction and its role in transcriptional regulation. We initially employed biophysical approach involving CD, UV and FRET to understand the role of polyamines (spermidine and spermine) on conformation, stability, molecular recognition of quadruplex and to investigate the effect of polyamines on quadruplex-Watson Crick duplex transition. Our study demonstrates that polyamines affect the c-MYC quadruplex conformation, perturb its recognition properties and delays duplex formation. The relative free energy difference (DeltaDeltaG degrees) between the duplex and quadruplex structure indicate that polyamines stabilize and favor c-MYC quadruplex over duplex. Further, we investigated the influence of polyamine mediated perturbation of this equilibrium on c-MYC expression. Our results suggest that polyamines induce structural transition of c-MYC quadruplex to a transcriptionally active motif with distinctive molecular recognition property, which drives c-MYC expression. These findings may allow exploiting quadruplex-polyamines interaction for developing antiproliferative strategies to combat aberrant gene expression.
@article{Kumar2009,
title = {Elevated polyamines induce c-{MYC} overexpression by perturbing quadruplex-{WC} duplex equilibrium.},
volume = {37},
issn = {1362-4962},
url = {internal-pdf:/1081832707yc overexpression.pdf http://nar.oxfordjournals.org/cgi/content/abstract/37/10/3321 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2691834&tool=pmcentrez&rendertype=abstract},
doi = {10.1093/nar/gkp196},
abstract = {The biological role of quadruplexes and polyamines has been independently associated with cancer. However, quadruplex-polyamine mediated transcriptional regulation remain unaddressed. Herein, using c-MYC quadruplex model, we have attempted to understand quadruplex-polyamine interaction and its role in transcriptional regulation. We initially employed biophysical approach involving CD, UV and FRET to understand the role of polyamines (spermidine and spermine) on conformation, stability, molecular recognition of quadruplex and to investigate the effect of polyamines on quadruplex-Watson Crick duplex transition. Our study demonstrates that polyamines affect the c-MYC quadruplex conformation, perturb its recognition properties and delays duplex formation. The relative free energy difference (DeltaDeltaG degrees) between the duplex and quadruplex structure indicate that polyamines stabilize and favor c-MYC quadruplex over duplex. Further, we investigated the influence of polyamine mediated perturbation of this equilibrium on c-MYC expression. Our results suggest that polyamines induce structural transition of c-MYC quadruplex to a transcriptionally active motif with distinctive molecular recognition property, which drives c-MYC expression. These findings may allow exploiting quadruplex-polyamines interaction for developing antiproliferative strategies to combat aberrant gene expression.},
number = {10},
journal = {Nucleic acids research},
author = {Kumar, Niti and Basundra, Richa and Maiti, Souvik},
month = jun,
year = {2009},
pmid = {19324889},
keywords = {\#nosource, Circular Dichroism, Fluorescence Resonance Energy Transfer, G-Quadruplexes, G-Quadruplexes: drug effects, Genes, Genetic, HeLa Cells, Humans, Nucleic Acid Denaturation, Promoter Regions, Proto-Oncogene Proteins c-myc, Proto-Oncogene Proteins c-myc: genetics, Spermidine, Spermidine: pharmacology, Spermine, Spermine: pharmacology, Thermodynamics, myc},
pages = {3321--31},
}
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