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Nucleic Acids Research Advance Access originally published online on March 26, 2009
Nucleic Acids Research 2009 37(10):3321-3331; doi:10.1093/nar/gkp196
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Nucleic Acids Research, 2009, Vol. 37, No. 10 3321-3331
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Elevated polyamines induce c-MYC overexpression by perturbing quadruplex–WC duplex equilibrium

Niti Kumar, Richa Basundra and Souvik Maiti*

Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India

*To whom correspondence should be addressed. Tel: +91 11 2766 6156; Fax: +91 11 2766 7471; Email: souvik{at}igib.res.in, souvik2maiti{at}yahoo.com

Received January 29, 2009. Revised March 8, 2009. Accepted March 10, 2009.

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 ({Delta}{Delta}G°) 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.


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