Shibata T, Nishinaka T, Mikawa T, Aihara H, Kurumizaka H, Yokoyama S, Ito Y
Cellular and Molecular Biology Laboratory, RIKEN, The Institute of Physical and Chemical Research, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8425-32. doi: 10.1073/pnas.111005198.
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.
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。异源双链体接头是在RecA/Rad51家族蛋白质介导的反应中，由切割后的亲本双链DNA衍生的单链区域（或尾巴）与另一个亲本双链DNA中的同源区域之间形成的。在这个反应中，RecA/Rad51家族蛋白质首先与单链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三维结构的研究揭示了一种新型的延伸DNA结构。这种结构在每个脱氧核糖的2'亚甲基部分与下一个碱基的芳香环之间存在疏水相互作用，这使得碱基能够通过糖环构象的相互转换而水平旋转。这种碱基旋转解释了在异源双链体接头形成过程中双链DNA和单链DNA之间同源性搜索和碱基对切换的机制。通过比较RNA基因组和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基因组的简单生物在遇到不利于其生存的条件时会诱导同源重组。这种延伸的DNA结构赋予原本化学和遗传稳定的双链DNA一种动态特性，使得基因片段重排而不干扰编码框架（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。
