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Golden jubilee of the DNA double helix

2003; Elsevier BV; Volume: 21; Issue: 4 Linguagem: Inglês

10.1016/s0167-7799(03)00031-3

0167-9430

Vadim V. Demidov,

DNA and Biological Computing

‘It has not escaped our notice that the specific pairing we have postulated [for DNA] immediately suggests a possible copying mechanism for the genetic material.’ J.D. Watson and F.H.C. Crick [1Watson J.D. Crick F.H.C. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid.Nature. 1953; 171: 737-738Crossref PubMed Scopus (8759) Google Scholar] ‘DNA is such an important molecule that it is almost impossible to learn too much about it.’ F.H. Crick et al. [2Crick F.H. et al.Is DNA really a double helix?.J. Mol. Biol. 1979; 129: 449-457Crossref Scopus (59) Google Scholar] ‘The DNA model of Watson and Crick looks like a diamond as big as the Ritz.’ M.D. Frank-Kamenetskii [3Frank-Kamenetskii M.D. Unraveling DNA: The Most Important Molecule of Life. Perseus Books, 1997Google Scholar] ‘Keeping up with the directions and applications of DNA is a never-ending job.’ I.E. Alcamo [4Alcamo I.E. DNA Technology: The Awesome Skill. Academic Press, 2000Google Scholar] This month commemorates a significant event in biotechnology ∗Note that while the DNA double helix celebrates its golden jubilee this year, one of its discoverers, James Dewey Watson (born on 6 April 1928 in Chicago, USA), commemorates his diamond jubilee – 75th birthday – the same year to a month.. In April 1953, a short report was published in Nature that described the famous double-helical structure of DNA, featuring the specific pairing of nucleobases (the complementarity principle) [1Watson J.D. Crick F.H.C. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid.Nature. 1953; 171: 737-738Crossref PubMed Scopus (8759) Google Scholar]. This remarkable discovery has stood up well to numerous experimental tests [2Crick F.H. et al.Is DNA really a double helix?.J. Mol. Biol. 1979; 129: 449-457Crossref Scopus (59) Google Scholar, 3Frank-Kamenetskii M.D. Unraveling DNA: The Most Important Molecule of Life. Perseus Books, 1997Google Scholar] and, nine years later, the researchers involved were awarded the Nobel Prize. Such a breakthrough in our understanding of genetic material dramatically changed every field of life sciences. Importantly, it gave birth to the DNA technology that has transformed many aspects of our lives by forming the basis of the modern pharmacogenomic, bioinformatic and biotechnological revolutions [3Frank-Kamenetskii M.D. Unraveling DNA: The Most Important Molecule of Life. Perseus Books, 1997Google Scholar, 4Alcamo I.E. DNA Technology: The Awesome Skill. Academic Press, 2000Google Scholar, 5Trifonov E.N. Earliest pages of bioinformatics.Bioinformatics. 2000; 16: 5-9Crossref Scopus (13) Google Scholar]. Owing to the seminal findings of Watson and Crick five decades ago, we now have robust hybridization- and PCR-based diagnostics [6Dangler C.A. Nucleic Acid Analysis. Principles and Bioapplications. Wiley-Liss, 1996Google Scholar], recombinant techniques and recombinant proteins [7Sambrook J. et al.Molecular Cloning: A Laboratory Manual. Cold Spring Harbour Laboratory Press, 1989Google Scholar], antisense (and, in the future, antigene) drugs [8Uhlmann E. Recent advances in the medicinal chemistry of antisense oligonucleotides.Curr. Opin. Drug Discov. Dev. 2000; 3: 203-213Google Scholar, 9Winters T.A. Gene targeted agents: new opportunities for rational drug development.Curr. Opin. Mol. Ther. 2000; 2: 670-681Google Scholar], gene therapy [10Anderson W.F. Gene therapy scores against cancer.Nat. Med. 2000; 6: 862-863Crossref Scopus (44) Google Scholar], and many more well-established biomolecular technologies, some of which have been reviewed in the pages of Trends in Biotechnology. The emerging fields of DNA nanotechnology [11Seeman N.C. Belcher A.M. Emulating biology: building nanostructures from the bottom up.Proc. Natl. Acad. Sci. 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DNA-based computer takes aim at genes.Science. 2002; 295: 951Crossref Scopus (13) Google Scholar] are also rather young offspring of the 50-year-old but still-productive DNA double helix. The recent deciphering of the human and other important genomes must also be mentioned in this context. The simplicity of the double-helical structure of DNA and the accuracy of interstrand DNA–DNA recognition via specific base pairing brought to life numerous nucleic acid analogs with modified sugar-phosphate backbones [19Uhlmann E. Peyman A. Antisense oligonucleotides: a new therapeutic principle.Chem. Rev. 1990; 90: 543-584Crossref Scopus (1556) Google Scholar]. DNA and RNA modifications significantly extended the practical potential of natural DNAs and RNAs, and finally inspired a Danish team, more than decade ago, to design a true DNA mimic – peptide nucleic acid (PNA) – featuring a totally unnatural pseudopeptide backbone [20Nielsen P.E. et al.Sequence selective recognition of DNA by strand displacement with a thymine-substituted polyamide.Science. 1991; 254: 1497-1500Crossref PubMed Scopus (2906) Google Scholar]. These promising artificial DNA-like molecules opened a completely new page in the field of biotechnological, pharmaceutical and diagnostic applications of nucleobase oligomers [21Ray A. Nordén B. Peptide nucleic acid (PNA): its medical and biotechnological applications and promise for the future.FASEB J. 2000; 14: 1041-1060PubMed Google Scholar, 22Demidov V.V. New kids on the block: emerging PNA-based DNA diagnostics.Expert Rev. Mol. Diagn. 2002; 2: 89-91Google Scholar, 23Demidov V.V. PNA comes of age: from infancy to maturity.Drug Discov. Today. 2002; 7: 153-155Crossref Scopus (19) Google Scholar]. In turn, they stimulated the quest for novel analogs and mimics [23Demidov V.V. PNA comes of age: from infancy to maturity.Drug Discov. Today. 2002; 7: 153-155Crossref Scopus (19) Google Scholar, 24Ganesh K.N. Nielsen P.E. Peptide nucleic acids. Analogs and derivatives.Curr. Org. Chem. 2000; 4: 916-928Crossref Scopus (133) Google Scholar, 25Braasch D.A. Corey D.R. Novel antisense and peptide nucleic acid strategies for controlling gene expression.Biochemistry. 2002; 41: 4503-4510Crossref PubMed Scopus (240) Google Scholar], which have given new opportunities for directed manipulation of genetic material. In recent years, significant efforts have been invested in the search for additional, non-Watson-Crick DNA base pairs to advance the stability and recognition specificity of the natural AT and GC base pairs [26Horlacher J. et al.Recognition by viral and cellular DNA polymerases of nucleosides bearing bases with nonstandard hydrogen bonding patterns.Proc. Natl. Acad. Sci. U.S.A. 1995; 92: 6329-6333Crossref Scopus (128) Google Scholar, 27Morales J.C. Kool E.T. Efficient replication between non-hydrogen-bonded nucleoside shape analogs.Nat. Struct. Biol. 1998; 5: 950-954Crossref Scopus (270) Google Scholar, 28Zimmermann N. et al.A novel silver(I)-mediated DNA base pair.J. Am. Chem. Soc. 2002; 124: 13684-13685Crossref Scopus (151) Google Scholar]. Furthermore, the Watson-Crick recognition principle has been supplemented by the ingenious concept of pseudocomplementarity, which makes it possible to selectively target a wide variety of arbitrary sequences directly within DNA duplexes [29Kutyavin I.V. et al.Oligonucleotides containing 2-aminoadenine and 2-thiothymine act as selectively binding complementary agents.Biochemistry. 1996; 35: 11170-11176Crossref Scopus (118) Google Scholar, 30Lohse J. et al.Double duplex invasion by peptide nucleic acid: a general principle for sequence-specific targeting of double-stranded DNA.Proc. Natl. Acad. Sci. U.S.A. 1999; 96: 11804-11808Crossref Scopus (274) Google Scholar, 31Senior K. Pseudocomplementary strategy strengthens PNA therapeutic potential.Drug Discov. Today. 2000; 5: 538-540Crossref Scopus (9) Google Scholar, 32Demidov V.V. et al.Kinetics and mechanism of the DNA double helix invasion by pseudocomplementary peptide nucleic acids.Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 5953-5958Crossref Scopus (101) Google Scholar]. Successful attempts to expand the genetic code have also been reported [33Sisido M. Hohsaka T. Introduction of specialty functions by the position-specific incorporation of nonnatural amino acids into proteins through four-base codon/anticodon pairs.Appl. Microbiol. Biotechnol. 2001; 57: 274-281Crossref Scopus (28) Google Scholar, 34Wang L. Schultz P.G. Expanding the genetic code.Chem. Commun. 2002; 1: 1-11Crossref Scopus (143) Google Scholar]. This is a promising approach for generating proteins with enhanced properties or even creating ‘synthetic organisms’ with particular functions. In addition to science and technology, omnipresent DNA penetrates essentially all corners of our everyday life, and has become a cultural icon and even a commodity [35Palevitz B.A. Awash in DNA news.The Scientist. 2002; 16: 8Google Scholar]. The double helix is such a striking symbol that it can be seen everywhere – on commercial posters, artworks (Fig. 1a) and postage stamps, on T-shirts and mugs, and even in the form of perfume bottles and in architecture (Fig. 1b). There is no doubt that the 21st century will be a new era for DNA, the molecular quintessence of life †For the history of ideas, the chronicle of the discovery of the double helix and biographies of the major figures in this adventure see [36Watson J.D. The Double Helix (A Norton Critical Edition). W.W. Norton and Company, 1980Google Scholar, 37Maddox B. Rosalind Franklin: The Dark Lady of DNA. Harper Collins Publishers, 2002Google Scholar]..