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A stretched conformation of DNA with a biological role?
Quarterly Reviews of Biophysics ( IF 7.2 ) Pub Date : 2017-08-10 , DOI: 10.1017/s0033583517000099
Niklas Bosaeus 1 , Anna Reymer 2 , Tamás Beke-Somfai 3 , Tom Brown 4 , Masayuki Takahashi 5 , Pernilla Wittung-Stafshede 1 , Sandra Rocha 1 , Bengt Nordén 6
Affiliation  

We have discovered a well-defined extended conformation of double-stranded DNA, which we call Σ-DNA, using laser-tweezers force-spectroscopy experiments. At a transition force corresponding to free energy change ΔG = 1·57 ± 0·12 kcal (mol base pair)−1 60 or 122 base-pair long synthetic GC-rich sequences, when pulled by the 3′−3′ strands, undergo a sharp transition to the 1·52 ± 0·04 times longer Σ-DNA. Intriguingly, the same degree of extension is also found in DNA complexes with recombinase proteins, such as bacterial RecA and eukaryotic Rad51. Despite vital importance to all biological organisms for survival, genome maintenance and evolution, the recombination reaction is not yet understood at atomic level. We here propose that the structural distortion represented by Σ-DNA, which is thus physically inherent to the nucleic acid, is related to how recombination proteins mediate recognition of sequence homology and execute strand exchange. Our hypothesis is that a homogeneously stretched DNA undergoes a ‘disproportionation’ into an inhomogeneous Σ-form consisting of triplets of locally B-like perpendicularly stacked bases. This structure may ensure improved fidelity of base-pair recognition and promote rejection in case of mismatch during homologous recombination reaction. Because a triplet is the length of a gene codon, we speculate that the structural physics of nucleic acids may have biased the evolution of recombinase proteins to exploit triplet base stacks and also the genetic code.

中文翻译:

具有生物学作用的 DNA 拉伸构象?

我们使用激光镊子力谱实验发现了定义明确的双链 DNA 扩展构象,我们称之为 Σ-DNA。在对应于自由能变化 Δ 的过渡力处G= 1·57 ± 0·12 kcal (mol 碱基对)-160 或 122 个碱基对长的合成富含 GC 序列,当被 3'-3' 链拉动时,会急剧转变为 1·52 ± 0·04 倍长的 Σ-DNA。有趣的是,在与重组酶蛋白(如细菌 RecA 和真核 Rad51)的 DNA 复合物中也发现了相同程度的延伸。尽管对所有生物有机体的生存、基因组维持和进化至关重要,但重组反应在原子水平上尚未得到理解。我们在此提出由 Σ-DNA 代表的结构扭曲,因此是核酸物理固有的,与重组蛋白如何介导序列同源性识别和执行链交换有关。我们的假设是,均匀拉伸的 DNA 经历“歧化”成由局部三联体组成的不均匀 Σ-形式- 像垂直堆叠的基地。这种结构可以确保提高碱基对识别的保真度,并在同源重组反应过程中发生错配时促进排斥。因为三联体是基因密码子的长度,我们推测核酸的结构物理学可能使重组酶蛋白的进化偏向于利用三联体碱基堆叠和遗传密码。
更新日期:2017-08-10
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