Biomedical subjects

A Kettani

Publications and source records attributed to A Kettani.

21 records · Page 2Linked to original sources

PubMed1997

Bombyx mori single repeat telomeric DNA sequence forms a G-quadruplex capped by base triads.

A combined NMR-molecular dynamics approach has been applied to determine the solution structure of a truncated analogue of the Bombyx mori telomeric d(TTAGG) single repeat sequence in Na+ cation-containing aqueous solution. The two-fold symmetric four-stranded d(TAGG) quadruplex contains two adjacent G(syn).G(syn).G(anti).G(anti) G-tetrads sandwiched between novel (T.A).A triads with individual strands having both a parallel and antiparallel neighbour around the quadruplex. The (T.A).A triad represents the first experimental verification of a base triad alignment which constitutes a key postulate in the recently proposed model of triad-DNA. Further, the (T.A).A triad is generated by positioning an A residue through hydrogen bonding in the minor groove of a Watson-Crick T.A base pair and includes a T-A platform related to an A-A platform recently observed in the structure of the P4-P6 domain of the Tetrahymena self splicing group I ribozyme. The novel architecture of the truncated Bombyx mori quadruplex structure sets the stage for the design and potential identification of additional base tetrads and triads that could participate in pairing alignments of multi-stranded DNA structures during chromosome association and genetic recombination.

Animals↗

PubMed1995

Solution structure of a DNA quadruplex containing the fragile X syndrome triplet repeat.

Both X-ray and NMR structural studies have defined the polymorphic nature of G-quadruplexes generated through mutual stacking of G.G.G.G tetrads by guanine rich telomeric sequences. Recently, the fragile X syndrome d(C-G-G)n triplet nucleotide repeat has been shown to form a stable quadruplex of undefined structure in monovalent cation solution. We have undertaken a structural characterization of the d(G-C-G-G-T3-G-C-G-G) undecanucleotide to elucidate the structural alignments associated with quadruplex formation by this oligomer which contains sequence elements associated with the fragile X syndrome triplet repeat. d(G-C-G-G-T3-G-C-G-G) in Na+ cation solution forms a quadruplex through dimerization of two symmetry related hairpins with the lateral connecting T3 loops positioned at opposite ends of the quadruplex. This novel NMR-molecular dynamics based solution structure contains internal G.C.G.C tetrads sandwiched between terminal G.G.G.G tetrads. Watson-Crick G.C base-pairs within individual hairpins dimerize through their major groove edges using bifurcated hydrogen bonds to form internal G(anti).C(anti).G(anti).C(anti) tetrads. Adjacent strands are anti-parallel to each other around the symmetric G-quadruplex which contains two distinct narrow and two symmetric wide grooves. By contrast, the terminal G-tetrads adopt G(syn).G(anti).G(syn).G(anti) alignments. The structure of the d(G-C-G-G-T3-G-C-G-G) quadruplex with its multi-layer arrangement of G.G.G.G and G.C.G.C tetrads greatly expands on our current knowledge of quadruplex folding topologies. Our results establish the pairing alignments that can be potentially utilized by the fragile X syndrome triplet repeat to form quadruplex structures through dimerization of hairpin stems. The formation of novel G.C.G.C tetrads through dimerization of Watson-Crick G.C base-pairs is directly relevant to the potential pairing alignments of helical stems in genetic recombination.

DNA↗

PubMed1993

Acid multimers of oligodeoxycytidine strands: stoichiometry, base-pair characterization, and proton exchange properties.

The structure recently proposed for the acid form of the oligonucleotide 5'-d(TC5) is a four-strand "tetrad" in which two parallel-stranded, base-paired duplexes are intimately associated, with their hemiprotonated C-C+ base pairs face-to-face and fully intercalated, in a so-called "i-motif" (Gehring et al., 1993). We use the amino and imino proton spectra to establish the structure and symmetry of the base pairs, properties which are a primary element in the resolution of the acid form describe above. The amino proton spectrum gives the best lower limit (8 x 10(4) s-1) on the rate of the imino proton jumping process which is responsible for the base-pair symmetry. The stoichiometry of the acid form of other deoxycytidine sequences is studied by gel filtration chromatography and in one case by an NMR equilibrium titration. In all cases, i.e., d(C12), d(T2C8T2), d(C4TC4), d(TC5), d(C5), d(C4), d(TC4), d(TC3T), and d(TC3), the acid form elutes as a tetramer. A single-strand component is also present in some cases. But no dimer is observed, except for some samples prepared by quenching from high temperatures. The characteristic H1'-H1' interresidue NOESY cross-peaks of the d(TC5) structure (Gehring et al., 1993) are also found in all the tetramers where they have been searched for, i.e., those of d(T2C8T2), d(C4TC4), d(TC3T), and d(TC3) (not shown), suggesting that these tetramers also are built on the i-motif and that such structures may be formed generally by strands containing a stretch of as little as three deoxycytidines. From the NMR titration of d(TC3), we derive a free energy of -7.6 kJ/mol per cytidine base pair for the formation of the tetramer from single strands. The free energy released by packing a base pair into the i-motif is comparable to that released in forming the base pair itself. Imino proton exchange is limited by base-pair opening, thanks to efficient intrinsic exchange catalysis: this explains the lack of effect of added catalysts. The base-pair lifetime is hundreds of times longer than in any DNA duplex, presumably due to the base-pair intercalation geometry. The variation of the lifetime along the sequence of the d(TC5) tetramer provides support for the recently proposed structure. The internal amino proton exchanges from the open state of the C-C+ pair, at a rate compatible with a pK of 9 appropriate for C+. But the external proton exchanges from the closed state, as with a pK of 17!(ABSTRACT TRUNCATED AT 400 WORDS)

Base Composition↗