Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA/Rad51-family proteins: A possible advantage of DNA over RNA as genomic material
Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA/Rad51-family proteins: A possible advantage of DNA over RNA as genomic material
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DOI：
10.1073/pnas.111005198
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发表时间：
2001-07
影响因子：
11.1
通讯作者：
T. Shibata;T. Nishinaka;T. Mikawa;H. Aihara;H. Kurumizaka;S. Yokoyama;Yutaka Ito
中科院分区：
文献类型：
--
作者：
T. Shibata;T. Nishinaka;T. Mikawa;H. Aihara;H. Kurumizaka;S. Yokoyama;Yutaka Ito
异源双链体接头是DNA基因组中同源基因重组的一般中间体。在由 RecA/Rad51 家族蛋白介导的反应中，来自切割的亲本双链 DNA 的单链区域（或尾部）与另一个亲本双链 DNA 中的同源区域之间形成异源双链体接头。在此反应中，RecA/Rad51 家族蛋白首先与单链 DNA 形成丝状复合物，然后与双链 DNA 相互作用以寻找同源性。对与大肠杆菌 RecA 或酿酒酵母 Rad51 结合的单链 DNA 的三维结构的研究揭示了一种新的延伸 DNA 结构。该结构包含每个脱氧核糖的2'亚甲基部分与后续碱基的芳香环之间的疏水相互作用，这使得碱基通过糖褶皱的相互转化而水平旋转。这种碱基旋转解释了异源双链体接头形成过程中双链和单链 DNA 之间的同源搜索和碱基对转换的机制。通过比较 RNA 基因组与 DNA 基因组的重组，支持了 2' 亚甲基碱基相互作用在异源双链体接头形成中的关键作用。一些具有DNA基因组的简单生物体在遇到不利于其生存的条件时会诱导同源重组。延伸的 DNA 结构赋予化学和遗传稳定的双链 DNA 动态特性，从而能够在不干扰编码框架的情况下进行基因片段重排（即蛋白质片段改组）。这些特性可能会给 DNA 带来广泛的进化优势。
Heteroduplex joints are general intermediates of homologous genetic recombination in DNA genomes. A heteroduplex joint is formed between a single-stranded region (or tail), derived from a cleaved parental double-stranded DNA, and homologous regions in another parental double-stranded DNA, in a reaction mediated by the RecA/Rad51-family of proteins. In this reaction, a RecA/Rad51-family protein first forms a filamentous complex with the single-stranded DNA, and then interacts with the double-stranded DNA in a search for homology. Studies of the three-dimensional structures of single-stranded DNA bound either to Escherichia coli RecA or Saccharomyces cerevisiae Rad51 have revealed a novel extended DNA structure. This structure contains a hydrophobic interaction between the 2′ methylene moiety of each deoxyribose and the aromatic ring of the following base, which allows bases to rotate horizontally through the interconversion of sugar puckers. This base rotation explains the mechanism of the homology search and base-pair switch between double-stranded and single-stranded DNA during the formation of heteroduplex joints. The pivotal role of the 2′ methylene-base interaction in the heteroduplex joint formation is supported by comparing the recombination of RNA genomes with that of DNA genomes. Some simple organisms with DNA genomes induce homologous recombination when they encounter conditions that are unfavorable for their survival. The extended DNA structure confers a dynamic property on the otherwise chemically and genetically stable double-stranded DNA, enabling gene segment rearrangements without disturbing the coding frame (i.e., protein-segment shuffling). These properties may give an extensive evolutionary advantage to DNA.