title: Beyond guanine quartets: cation-induced formation of homogenous and chimeric DNA tetraplexes incorporating iso-guanine and guanine.
abstract: BACKGROUND
  iso-Guanine (iso-G) is the purine component of an isomeric Watson-Crick base pair that may have existed prebiotically. By comparing the abiotic molecular recognition properties of iso-G and its complement, iso-cytosine (iso-C), with those of genomic nucleotide bases, it may be possible to explain the exclusion of the iso-G-iso-C base pair from modern genomes. Whether a nucleobase forms quartets may have a key role in determining its functionality. Biotically, nucleic acid tetraplexes have been implicated in cellular functions; prebiotically, tetraplexes would probably interfere with replication. Recently, in vitro selection has yielded receptors and catalysts that incorporate G quartets. The versatility of these structures could be enhanced by expanding the range of bases that can form the quartet motif.
  
  
  RESULTS
  Native polyacrylamide gel electrophoresis of oligonucleotides bearing runs of iso-G provides strong support for tetraplex formation via cation-promoted DNA strand association. In particular, when strands of different lengths bearing the same iso-G tetrad recognition element were combined, five bands were observed after electrophoresis, corresponding to all possible heterotetraplexes with parallel strand alignment. An analogous experiment with a mixture of strands bearing iso-G or G tetrad recognition domains supports the existence of mixed iso-G/G tetraplexes with antiparallel strand alignment at chimeric junctions. iso-G tetraplex and quartet structure has also been probed by a photo-crosslinking experiment, ultra-violet spectroscopy and theoretical calculations.
  
  
  CONCLUSIONS
  As iso-G and G both have a marked tendency to form tetraplexes, their tandem inclusion in genetic material may be problematic, leading to double-stranded DNA half composed of bases that have a tendency to auto-associate. The resulting density of 'selfish' bases could undermine Watson-Crick pair formation, especially in a prebiotic context devoid of enzymes. Nevertheless, the ability of iso-G to form mixed quartets with G may provide a basis for altering the properties of tetraplexes in the domain of artificial receptors or catalysts from in vitro selections.
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521, USA.
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.forename: J C
authors.initials: JC
authors.lastname: Chaput
authors.forename: C
authors.initials: C
authors.lastname: Switzer
mesh_terms: D002412:Cations; D003432:Cross-Linking Reagents; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D016678:Genome; D006147:Guanine / Q000378:metabolism*; D016296:Mutagenesis; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D010777:Photochemistry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002412:Cations; D003432:Cross-Linking Reagents; D009841:Oligonucleotides; C093270:isocytosine; D006147:Guanine; D003596:Cytosine; D004247:DNA; C008183:isoguanine