Structural polymorphism of telomeric DNA regulated by pH and divalent cation
Structural polymorphism of telomeric DNA regulated by pH and divalent cation
复制标题
DOI：
10.1081/ncn-120019528
复制
发表时间：
2003-01-01
影响因子：
1.3
通讯作者：
Sugimoto, N
中科院分区：
文献类型：
--
作者：
Miyoshi, D;Matsumura, S;Sugimoto, N
DNA寡核苷酸可以形成多链结构，如双链体、三链体和四链体，而双螺旋结构通常被认为是DNA寡核苷酸的典型结构。富含鸟嘌呤或胞嘧啶的寡核苷酸在体内存在于端粒、着丝粒和其他生物学重要序列中，在体外可形成四链G-四链体和I-基序结构。本文研究了pH和阳离子对d（G（4）T（4）G（4））和d（C（4）A（4）C（4））的结构和稳定性的影响。在不同pH值的DNA的CD光谱和热熔解曲线表明，酸性条件下诱导一个稳定的，I-基序结构。pH值对d（C（4）A（4）C（4））的G-四链体结构和稳定性没有影响。d（G（4）T（4）G（4））和d（C（4）A（4）C（4））的1：1混合物的CD光谱表明酸性条件抑制d（G（4）T（4）G（4））和d（C（4）A（4）C（4））之间的双链体形成。等温滴定量热法测量的双链体形成在不同的pH值也定量表明，酸性条件抑制双链体的形成。另一方面，在无Ca ~（2+）和有Ca ~（2+）存在下，DNA的CD谱和热熔解曲线表明，Ca ~（2+）诱导d（G（4）T（4）G（4））的平行G-四链体结构，然后抑制双链体的形成。这些结果导致的结论是，pH值和共存的阳离子可以诱导和调节寡核苷酸的结构多态性，其中它们形成G-四链体，I-基序，和双链体取决于条件。因此，本文报道的结果表明，pH值和共存的阳离子在生物过程中的关键作用，通过调节的双链体和四链体结构的鸟嘌呤丰富或胞嘧啶丰富的寡核苷酸在体内的构象切换。
DNA oligonucleotides can form multi-stranded structures such as a duplex, triplex, and quadruplex, while the double helical structure is generally considered as the canonical structure of DNA oligonucleotides. Guanine-rich or cytosine-rich oligonucleotides, which are observed in telomere, centromere, and other biologically important sequences in vivo, can form four-stranded G-quadruplex and I-motif structures in vitro. In this study, we have investigated the effects of pH and cation on the structures and their stabilities of d(G(4)T(4)G(4)) and d(C(4)A(4)C(4)). The CD spectra and thermal melting curves of DNAs at various pHs demonstrated that acidic conditions induced a stable, I-motif structure. of d(C(4)A(4)C(4)), while the pH value did not affect the G-quadruplex structure and stability of d(G(4)T(4)G(4)). The CD spectra of the 1: 1 mixture of d(G(4)T(4)G(4)) and d(C(4)A(4)C(4)) indicated that the acidic conditions inhibit the duplex formation between d(G(4)T(4)G(4)) and d(C(4)A(4)C(4)). Isothermal titration calorimetry measurements of the duplex formation at various pHs also quantitatively indicated that the acidic conditions inhibit the duplex formation. On the other hand, the CD spectra and thermal melting curves of DNAs in the absence and presence of Ca2+ indicated that Ca2+ induces a parallel G-quadruplex sructure of d(G(4)T(4)G(4)) and then inhibits the duplex formation. These results lead to the conclusion that both the pH and coexisting cation can induce and regulate the structural polymorphisms the oligonucleotides in which they form the G-quadruplex, I-motif, and duplex depending on the conditions. Thus, the results reported here indicate pivotal roles of pH and coexisting cations in biological processes by regulating the conformational switching between the duplex and quadruplexes structures of the guanine-rich or cytosine-rich oligonucleotides in vivo.