THEORETICAL-ANALYSIS OF TRANSITIONS BETWEEN B-CONFORMATIONS AND Z-CONFORMATIONS IN TORSIONALLY STRESSED DNA

THEORETICAL-ANALYSIS OF TRANSITIONS BETWEEN B-CONFORMATIONS AND Z-CONFORMATIONS IN TORSIONALLY STRESSED DNA
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DOI:
10.1038/286637a0
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发表时间:
1980-01-01
期刊:
影响因子:
64.8
通讯作者:
BENHAM, CJ
BENHAM, CJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BENHAM, CJ

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最近,基于对六核苷酸的晶体学分析,提出了一种称为Z-DNA的新结构,用于交替的poly(dG-dC)·poly(dG-dC)序列1。Z型是一种左手双螺旋,每圈含有12个碱基对。相比之下,沃森-克里克B型螺旋被认为每转有10.4对右旋螺旋2,3,8。在聚(dG-dC)·聚(dG-dC)4中观察到了盐诱导的协同构象转变,该转变被解释为介于B型(低盐)和Z型(高盐)之间1。我们现在分析的可能性,这种转变可能发生在敏感的序列在生理条件下的结果所施加的扭转应力的超螺旋。由于体内DNA通常以负超螺旋(因此是欠缠绕)状态发生,因此这些转变可以发挥重要的生物学功能。热力学和统计力学理论的应力诱导的两个状态转变已经开发previously 5,6。在这里,我们将这些理论应用于适当的碱基序列区域中的B型和Z型之间的转换。假设无应力的双链体完全是B-形式,我们表明,当分子被约束到下缠绕,敏感区域可能会转变为Z-形式,从而吸收大部分的扭转变形。有趣的是,这种转变相对独立于温度。
Recently, a new structure called Z-DNA has been proposed for alternating poly(dG-dC)·poly(dG-dC) sequences based on crystallographic analysis of the hexanucleotide1. The Z-form is a left-handed double helix containing 12 base pairs per turn. In contrast, the Watson–Crick B-form helix is thought to have 10.4 pairs per turn of right-handed helix2,3,8. A cooperative, salt-induced conformational transition has been observed in poly(dG-dC)·poIy(dG-dC)4, which has been interpreted as being between the B-form (low salt) and the Z-form (high salt)1. We now analyse the possibility that such transitions could occur in susceptible sequences in physiological conditions as a consequence of the torsional stresses imposed by superhelicity. Asin vivoDNA commonly occurs in a negatively supercoiled, hence underwound, state, these transitions could serve important biological functions. Both thermodynamic and statistical mechanical theories of stress-induced two-state transitions have been developed previously5,6. Here we apply these theories to transitions between the B-form and the Z-form in regions of appropriate base sequence. Assuming that the unstressed duplex is entirely B-form, we show that when the molecule is constrained to be underwound, susceptible regions may transform to the Z-form, thereby absorbing most of the torsional deformation. Interestingly, this transition is relatively independent of temperature.