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The following HTML text is provided to enhance online readability. Many aspects of typography translate only awkwardly to HTML. Please use the page image as the authoritative form to ensure accuracy. ColloquiumHomologous 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 materialTakehiko Shibata*†‡, Taro Nishinaka*§, Tsutomu Mikawa*†, Hideki Aihara*¶||, Hitoshi Kurumizaka†,††, Shigeyuki Yokoyama¶††, and Yutaka Ito*† *Cellular and Molecular Biology Laboratory, RIKEN (The Institute of Physical and Chemical Research), Hirosawa 2–1, Wako-shi, Saitama 351–0198, Japan; †CREST, JST (Japan Science and Technology Corporation), ¶Department of Biophysics and Biochemistry, The Graduate School of Science, The University of Tokyo, Tokyo 113, Japan; and ††Cellular Signaling Laboratory, RIKEN Harima Institute at SPring-8, 1–1–1 Kouto, Mikazuki, Sayo, Hyogo 679–5148, Japan 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. base-pair switch | homologous pairing | strand exchange | NMR | three-dimensional molecular structure DNA as a General Molecular Carrier of Genetic InformationGenomic information generally is carried by double-stranded DNA. The double-stranded DNA structure discovered by Watson and Crick clearly explains the mechanisms of heredity, which include both the encoding of genetic information and its duplication as chemical properties of the molecule (1). In addition, the double-stranded structure enables cellular systems to recognize, as structural irregularities, erroneously incorporated nucleotides or lesions in bases, sugars, or the backbone strand, and to correct these errors by using the partner strand as a template. The genetic stability and the chemical inactivity of double-stranded DNA have been regarded as favorable molecular properties for its role as the carrier of genomic information. Evolution, which is a general attribute of the genome as well, has resulted in a variety of organisms, whose diversity arose not only as a result of changes in the genomic information, but also as a result of increased content and complexity. The faithful duplication and repair exhibited by the double-stranded DNA structure would seem to be incompatible with the process of evolution. Thus, evolution has been explained by the occurrence of “errors” during DNA replication and repair, which were subsequently stabilized as mutations and selected for by the process of natural selection (e.g., ref. 2). If mutations played a key function in evolution, organisms with RNA genomes, which show a higher mutation frequency than DNA genomes, would have evolved into higher organisms much faster than those with DNA genomes, but this is not the case. One explanation why organisms with RNA genomes did not evolve beyond the level of viruses is that their high rate of spontaneous mutation prevents the maintenance of a genome of the required complexity. The low level of successful mutations in the DNA genome is unlikely to be caused by its chemical stability, but rather by correction systems acquired during evolution, such as proofreading and repair systems for mismatches and lesions in DNA (3, 4). The double-stranded structure required for repair or correction is also not a specific property of DNA, because the genomic RNA of some viruses is also double-stranded. Moreover, it is generally believed that primordial creatures consisted of RNA, and that RNA as a molecular carrier of genomic information eventually was supplanted by This paper results from the National Academy of Sciences colloquium, “Links Between Recombination and Replication: Vital Roles of Recombination,” held November 10–12, 2000, in Irvine, CA. Abbreviation: NOE, nuclear Overhauser effect.
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