DNA的延伸构象具有生物学作用?

IF 7.2 2区 生物学 Q1 BIOPHYSICS Quarterly Reviews of Biophysics Pub Date : 2017-01-01 DOI:10.1017/S0033583517000099
Niklas Bosaeus, Anna Reymer, Tamás Beke-Somfai, Tom Brown, Masayuki Takahashi, Pernilla Wittung-Stafshede, Sandra Rocha, Bengt Nordén
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引用次数: 15

摘要

我们利用激光镊子力谱实验,发现了一种定义明确的双链DNA延伸构象,我们称之为Σ-DNA。在与自由能变化相对应的过渡力ΔG = 1.57±0.12 kcal (mol碱基对)-1 60或122碱基对长的合成富gc序列,在3'-3'链的拉动下,急剧过渡到1.52±0.04倍长的Σ-DNA。有趣的是,在重组酶蛋白的DNA复合体中也发现了相同程度的延伸,如细菌的RecA和真核生物的Rad51。尽管重组反应对所有生物的生存、基因组维持和进化至关重要,但在原子水平上尚未被理解。我们在此提出Σ-DNA所代表的结构扭曲,这是核酸固有的物理特性,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,一个均匀拉伸的DNA经历了“歧化”,变成了一个不均匀的Σ-form,由三组局部b型垂直堆叠的碱基组成。这种结构可以提高碱基对识别的保真度,并促进同源重组反应中不匹配的排斥反应。由于三联体是基因密码子的长度,我们推测核酸的结构物理可能偏向于重组酶蛋白的进化,以利用三联体碱基堆栈和遗传密码。
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A stretched conformation of DNA with a biological role?

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.

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来源期刊
Quarterly Reviews of Biophysics
Quarterly Reviews of Biophysics 生物-生物物理
CiteScore
12.90
自引率
1.60%
发文量
16
期刊介绍: Quarterly Reviews of Biophysics covers the field of experimental and computational biophysics. Experimental biophysics span across different physics-based measurements such as optical microscopy, super-resolution imaging, electron microscopy, X-ray and neutron diffraction, spectroscopy, calorimetry, thermodynamics and their integrated uses. Computational biophysics includes theory, simulations, bioinformatics and system analysis. These biophysical methodologies are used to discover the structure, function and physiology of biological systems in varying complexities from cells, organelles, membranes, protein-nucleic acid complexes, molecular machines to molecules. The majority of reviews published are invited from authors who have made significant contributions to the field, who give critical, readable and sometimes controversial accounts of recent progress and problems in their specialty. The journal has long-standing, worldwide reputation, demonstrated by its high ranking in the ISI Science Citation Index, as a forum for general and specialized communication between biophysicists working in different areas. Thematic issues are occasionally published.
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