Energetics of Z-DNA Binding Protein-Mediated Helicity Reversals in DNA, RNA, and DNA-RNA Duplexes

Energetics of Z-DNA Binding Protein-Mediated Helicity Reversals in DNA, RNA, and DNA-RNA Duplexes
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DOI:
10.1021/jp409862j
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发表时间:
2013-11-07
影响因子:
3.3
通讯作者:
Hohng, Sungchul
Hohng, Sungchul
中科院分区:
化学3区
文献类型:
--
作者:
Bae, Sangsu;Kim, Yuyoung;Hohng, Sungchul

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Z-DNA 结合蛋白 (ZBP) 特异性识别并稳定左手双螺旋,包括 Z-DNA 和 Z-RNA。然而,由于批量研究的技术限制,ZBP稳定Z型的能量学从未得到表征,导致对ZBP在分子水平上的运作机制的理解尚不清楚。在这里,我们使用单分子荧光共振能量转移(FRET)来确定 ZBP 对 DNA、RNA 和 DNA-RNA 双链体的 Z 型稳定的能量学,揭示 B-Z 或 A-Z 连接的形成主导 Z 型稳定的热力学和动力学。此外,与一般假设相反,由于 DNA-RNA 杂合体中的连接能量大大降低,Z 型在 DNA-RNA 杂合体双链体中形成最有效且最快速。
Z-DNA binding proteins (ZBPs) specifically recognize and stabilize left-handed double helices, including Z-DNA and Z-RNA. However, the energetics of Z-form stabilization by ZBPs have never been characterized due to the technical limitations of bulk studies, resulting in an unclear understanding of the ZBP operational mechanism at the molecular level. Here, we use single-molecule fluorescence resonance energy transfer (FRET) to determine the energetics of Z-form stabilization by ZBP for DNA, RNA, and DNA-RNA duplexes, revealing that the formation of B-Z or A-Z junctions dominates the thermodynamics and kinetics of Z-form stabilization. Furthermore, in contrast to general assumptions, the Z-form is most efficiently and most rapidly formed in the DNA-RNA hybrid duplex due to the greatly reduced junction energy in the DNA-RNA hybrid.