CATION-DEPENDENT TRANSITION BETWEEN THE QUADRUPLEX AND WATSON-CRICK HAIRPIN FORMS OF D(CGCG3GCG)
CATION-DEPENDENT TRANSITION BETWEEN THE QUADRUPLEX AND WATSON-CRICK HAIRPIN FORMS OF D(CGCG3GCG)
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DOI：
10.1021/bi00118a028
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发表时间：
1992-01-28
期刊：
影响因子：
2.9
通讯作者：
BAILEY, C
中科院分区：
文献类型：
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作者：
HARDIN, CC;WATSON, T;BAILEY, C
DNA寡核苷酸d（CGCG 3GCG）可以形成沃森-克里克（WC）发夹结构或含有六个G-四重碱基对组装体的平行链四链体结构。这些形式和单链之间的交换可以使用圆二色性（CD）监测。NMR结果验证了特定CD带分别归属于四链体和发夹种类。阳离子稳定四链体的顺序为K+ > Ca 2 + > Na+ > Mg 2 + > Li+和K+ > Rb+ > Cs+，表明K+具有形成复合物的最佳离子半径，并且离子电荷影响离子诱导稳定的程度。四链体在微摩尔DNA浓度的40 mM K+存在下是稳定的，并且当以毫摩尔DNA浓度制备然后稀释到含有40 mM Na+的缓冲液中时，可以动力学捕获为亚稳态形式。从发夹到四链体的平衡逆转所需的K+浓度随着DNA浓度的增加而急剧下降。四链体具有不寻常的pK（a）约。6.8，表明C.C+碱基对可能正在形成。该系统提供了对[“G4-DNA”.ion]复合物的一些详细结构特征的了解和最近提出的“钠-钾构象转换”的实验模型[Sen，D.，&吉尔伯特，W.（1988）Nature 334，364-366; Sen，D.，&吉尔伯特，W.（1990）Nature 344，410-414]。这些结果可能有助于解释缺乏胞苷残基的G-丰富的端粒DNA，并建议，甲基化的GC-丰富的双链体DNA在“GpC岛”可能会诱导四链体形成异染色质结构域内，导致可逆的染色体凝聚。
The DNA oligonucleotide d(CGCG3GCG) can form either a Watson-Crick (WC) hairpin or a parallel-stranded quadruplex structure containing six G-quartet base pair assemblies. The exchange between these forms and single strands can be monitored using circular dichroism (CD). NMR results verified the assignment of specific CD bands to quadruplex and hairpin species, respectively. Cations stabilize the quadruplex in the order K+ > Ca2+ > Na+ > Mg2+ > Li+ and K+ > Rb+ > Cs+, indicating that K+ has an optimum ionic radius for complex formation and that ionic charge affects the extent of ion-induced stabilization. The quadruplex is stable in the presence of 40 mM K+ at micromolar DNA concentration and can be kinetically trapped as a metastable form when prepared at millimolar DNA concentration and then diluted into buffer containing 40 mM Na+. The concentration of K+ required to reverse the equilibrium from the hairpin to the quadruplex decreases sharply with increased DNA concentration. The quadruplex has an unusual pK(a) of ca. 6.8, indicating that C.C+ base pairs are probably forming. This system provides insights into some of the detailed structural characteristics of a ["G4-DNA".ion] complex and an experimental model for the recently proposed "sodium-potassium conformational switch" [Sen, D., & Gilbert, W. (1988) Nature 334, 364-366; Sen, D., & Gilbert, W. (1990) Nature 344, 410-414]. These results may help to explain the lack of cytidine residues in G-rich telomeric DNAs and suggest that methylation of GC-rich duplex DNAs in "GpC islands" may induce quadruplex formation within heterochromatin domains, resulting in reversible chromosomal condensation.