Biophysical Characterization of the Human Telomeric (TTAGGG)4 Repeat in a Potassium Solution

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• 作者：Cosimo Antonacci ; Jonathan B. Chaires ; Richard D. Sheardy
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：April 17, 2007
• 年：2007
• 卷：46
• 期：15
• 页码：4654 - 4660
• 全文大小：256K
• 年卷期：v.46,no.15(April 17, 2007)
• ISSN：1520-4995

文摘

Quadruplex structures arise from four coplanar G bases arranged in a Hoogsteen base pairingmotif to create a central pore that can coordinate cations. The termini of eukaryotic chromosomes containstructures, known as telomeres, which are capable of forming quadruplex structures. Quadruplexes havebeen implicated in a variety of disease states, including cancer. The literature seems to agree that thehuman telomeric repeat containing four stretches of three guanines displays conformational states that aredifferent in the presence of Na⁺ and K⁺ and an unknown number of species involved in the quadruplexto single strand transition. Using circular dichroism spectroscopy, differential scanning calorimetry, andsingular-value decomposition, the number of species present in the dissociation process is assessed. Theresults indicate that three species exist in equilibria during the melting process. We present a model forthe heat-induced denaturation from the folded to the unfolded state, whereby the hybrid parallel-antiparallelquadruplex undergoes a transition to an unknown intramolecular intermediate followed by a transition toa single strand.