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

Molecules

Katherine L. Hayden¹ 

[1]Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA

[2] E-Mail:

关键词: telomere;    G-quadruplex;    stability;    circular dichroism (CD);    differential scanning calorimetry (DSC);    pressure perturbation calorimetry (PPC);    osmolyte perturbation;   

DOI  :  10.3390/molecules19022286

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.