A two-stranded template-based approach to G.(C-A) triad formation: designing novel structural elements into an existing DNA framework.
We have designed a DNA sequence, d(G-G-G-T-T-C-A-G-G), which dimerizes to form a 2-fold symmetric G-quadruplex in which G(syn). G(anti).G(syn).G(anti) tetrads are sandwiched between all trans G. (C-A) triads. The NMR-based solution structural analysis was greatly aided by monitoring hydrogen bond alignments across N-H...N and N-H...O==C hydrogen bonds within the triad and tetrad, in a uniformly ((13)C,(15)N)-labeled sample of the d(G-G-G-T-T-C-A-G-G) sequence. The solution structure establishes that the guanine base-pairs with the cytosine through Watson-Crick G.C pair formation and with adenine through sheared G.A mismatch formation within the G.(C-A) triad. A model of triad DNA was constructed that contains the experimentally determined G.(C-A) triad alignment as the repeating stacked unit.
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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A
Kettani
G
G
Basu
A
A
Gorin
A
A
Majumdar
E
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Skripkin
D J
DJ
Patel
D020137:Base Pair Mismatch / Q000235:genetics; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D054856:G-Quadruplexes; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D010758:Phosphorus / Q000737:chemistry / Q000378:metabolism; D011522:Protons; D013329:Structure-Activity Relationship; D013698:Templates, Genetic
D011522:Protons; D010758:Phosphorus; D004247:DNA