Pedroso Ilene M, Duarte Luis F, Yanez Giscard, Baker Asmaa M, Fletcher Terace M
Department of Biochemistry and Molecular Biology, University of Miami, School of Medicine, P.O. Box 016129 (R629), Miami, FL 33101-6129, USA.
Biochem Biophys Res Commun. 2007 Jun 22;358(1):298-303. doi: 10.1016/j.bbrc.2007.04.126. Epub 2007 Apr 27.
Human telomeric DNA forms G-quadruplex secondary structures, which can inhibit telomerase activity and are targets for anti-cancer drugs. Here we show that Sr(2+) can induce human telomeric DNA to form both inter- and intramolecular structures having characteristics consistent with G-quadruplexes. Unlike Na(+) or K(+), Sr(2+) facilitated intermolecular structure formation for oligonucleotides with 2 to 5 5'-d(TTAGGG)-3' repeats. Longer 5'-d(TTAGGG)-3' oligonucleotides formed exclusively intramolecular structures. Altering the 5'-d(TTAGGG)-3' to 5'-d(TTAGAG)-3' in the 1st, 3rd, or 4th repeats of 5'-d(TTAGGG)(4)-3' stabilized the formation of intermolecular structures. However, a more compact, intramolecular structure was still observed when the 2nd repeat was altered. Circular dichroism spectroscopy results suggest that the structures were parallel-stranded, distinguishing them from similar DNA sequences in Na(+) and K(+). This study shows that Sr(2+), promotes parallel-stranded, inter- and intramolecular G-quadruplexes that can serve as models to study DNA substrate recognition by telomerase.
人类端粒DNA形成G-四链体二级结构，其可抑制端粒酶活性，是抗癌药物的作用靶点。在此我们表明，Sr(2+)可诱导人类端粒DNA形成具有与G-四链体一致特征的分子间和分子内结构。与Na(+)或K(+)不同，Sr(2+)促进了具有2至5个5'-d(TTAGGG)-3'重复序列的寡核苷酸的分子间结构形成。更长的5'-d(TTAGGG)-3'寡核苷酸仅形成分子内结构。在5'-d(TTAGGG)(4)-3'的第1、3或4个重复序列中将5'-d(TTAGGG)-3'改变为5'-d(TTAGAG)-3'可稳定分子间结构的形成。然而，当第2个重复序列改变时，仍观察到更紧凑的分子内结构。圆二色光谱结果表明，这些结构为平行链结构，这使其与Na(+)和K(+)中的类似DNA序列区分开来。本研究表明，Sr(2+)促进平行链的分子间和分子内G-四链体形成，其可作为研究端粒酶对DNA底物识别的模型。
