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Molecules 2014, 19(2), 2286-2298; doi:10.3390/molecules19022286
Article

Addition of Bases to the 5'-end of Human Telomeric DNA: Influences on Thermal Stability and Energetics of Unfolding

1
 and 1,2,*
Received: 29 September 2013; in revised form: 24 January 2014 / Accepted: 7 February 2014 / Published: 21 February 2014
(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)
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Abstract: Telomeric DNA has been intensely investigated for its role in chromosome protection, aging, cell death, and disease. In humans the telomeric tandem repeat (TTAGGG)n is found at the ends of chromosomes and provides a novel target for the development of new drugs in the treatment of age related diseases such as cancer. These telomeric sequences show slight sequence variations from species to species; however, each contains repeats of 3 to 4 guanines allowing the G-rich strands to fold into compact and stable nuclease resistant conformations referred to as G-quadruplexes. The focus of this manuscript is to examine the effects of 5'-nucleotides flanking the human telomeric core sequence 5'-AGGG(TTAGGG) 3-3' (h-Tel22). Our studies reveal that the addition of the 5'-flanking nucleotides (5'-T, and 5'-TT) results in significant changes to the thermodynamic stability of the G-quadruplex structure. Our data indicate that the observed changes in stability are associated with changes in the number of bound waters resulting from the addition of 5'-flanking nucleotides to the h-Tel22 sequence as well as possible intermolecular interactions of the 5' overhang with the core structure.
Keywords: telomere; G-quadruplex; stability; circular dichroism (CD); differential scanning calorimetry (DSC); pressure perturbation calorimetry (PPC); osmolyte perturbation telomere; G-quadruplex; stability; circular dichroism (CD); differential scanning calorimetry (DSC); pressure perturbation calorimetry (PPC); osmolyte perturbation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Hayden, K.L.; Graves, D.E. Addition of Bases to the 5'-end of Human Telomeric DNA: Influences on Thermal Stability and Energetics of Unfolding. Molecules 2014, 19, 2286-2298.

AMA Style

Hayden KL, Graves DE. Addition of Bases to the 5'-end of Human Telomeric DNA: Influences on Thermal Stability and Energetics of Unfolding. Molecules. 2014; 19(2):2286-2298.

Chicago/Turabian Style

Hayden, Katherine L.; Graves, David E. 2014. "Addition of Bases to the 5'-end of Human Telomeric DNA: Influences on Thermal Stability and Energetics of Unfolding." Molecules 19, no. 2: 2286-2298.



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