Hairpin structures in DNA containing arabinofuranosylcytosine. A combination of nuclear magnetic resonance and molecular dynamics

Pieters, Jane M. L.; Vroom, Erik de; Marel, Gijs A. van der; Boom, Jacques H. van; Koning, T. M. G.; Kaptein, Robert; Altona, C.

doi:10.1021/bi00455a029

Cited by 53 publications

(58 citation statements)

References 51 publications

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“…The latter finding contradicts the results of earlier computational simulations that suggested a preference for the C2′-endo pucker by arabinose (22). Although the above experimental data are consistent with similar conformational tendencies by FANA and ANA, the conformation of ANA was demonstrated to vary significantly depending on the geometry of the parent duplex (23)(24)(25)(26)(27)(28)(29).…”

contrasting

confidence: 71%

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

Sarkhel

Wilds

et al. 2006

Biochemistry

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2′-Deoxy-2′-fluoro-arabinonucleic acid (FANA) and arabinonucleic acid (ANA) paired to RNA are substrates of RNase H. The conformation of the natural DNA/RNA hybrid substrates appears to be neither A-form nor B-form. Consistent with this, the conformations of FANA and ANA were found to be intermediate between the A-and B-forms. However, FANA opposite RNA is preferred by RNase H over ANA, and the RNA affinity of FANA considerably exceeds that of ANA. By investigating the conformational boundaries of FANA and ANA residues in crystal structures of A-and B-form DNA duplexes at atomic resolution, we demonstrate that FANA and ANA display subtle conformational differences. The structural data provide insight into the structural requirements at the catalytic site of RNase H. They also allow conclusions with regard to the relative importance of stereoelectronic effects and hydration as modulators of RNA affinity.

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contrasting

confidence: 71%

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

Sarkhel

Wilds

et al. 2006

Biochemistry

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“…At this point, it is interesting to compare the present results with those obtained for the mini-hairpins formed by d(mCGmCGTGmCG) and d(CGC"TAGCG) [5,36]. In these sequences, mC denotes a cytidine methylated at the C5 position and C" represents a cytidine in which the deoxyribose sugar is replaced by an arabinose sugar.…”

Section: Comparison With Other Hairpinsmentioning

confidence: 74%

“…e--(+-ccf-flyt instead of e'-C--a--fl-y+. nucleotide form a base pair, but in this case the second loop residue (the thymine) is turned into the minor groove [36] as in the d(ATCCTATTTATAGGAT) molecule. The presence of the arabinose sugar may be surmised to play a predominant role in inducing this effect, but the d(ATCCTATTTATAG-GAT) hairpin is an example that this may occur in an all deoxyribose-phosphate backbone as well.…”

Section: The Hairpin-loop Structurementioning

confidence: 99%

The three‐dimensional structure of a DNA hairpin in solution

Blommers¹,

Ven²,

Marel

et al. 1991

European Journal of Biochemistry

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The hairpin formed by d(ATCCTATTTATAGGAT) was studied by means of two-dimensional NMR spectroscopy and conformational analysis. Almost all 'H resonances of the stem region could be assigned, while the 'H and 31P spectra of the loop region were interpreted completely; this includes the stereospecific assignment of the H5' and H5" resonances. The derivation of the detailed loop structure was carried out in a stepwise fashion including some improved and new methods for structure determination from NMR data. In the first step, the mononucleotide structures were examined. The conformational space available to the mononucleotide was scanned systematically by varying the glycosidic torsion angle and pseudorotational parameters. Each generated conformer was tested against the experimental J coupling constants and NOE parameters. In the following stage, the structures of dinucleotides and longer fragments were derived. Inter-residue distances between protons were calculated by means of a procedure in which the simulated NOEs, obtained via a relaxation-matrix approach, were fitted to the experimental NOEs without the introduction of a molecular model. In addition, the backbone torsion angles fl, y and c were deduced from homocoupling and heterocoupling constants. These data served as constraints in the next step, in which the loop sequence was subjected to a multi-conformer generation procedure. The resulting structures were tested against the mentioned constraints and disregarded if these constraints were violated. This yielded a family of structures for the loop region, confined to a relatively narrow conformational space. A representative conformation was subsequently docked on a B-type stem which fulfilled the structural constraints (derived from the NMR experiments for the stem region) to yield the hairpin structure. Results obtained from subsequent restrained-molecular-mechanics as well as free-molecular-mechanics calculations are in accordance with those obtained by means of the analysis described above.The structure of the hairpin loop is a compactly folded conformation and the first base of the central TTTA region forms a Hoogsteen T-A pair with the fourth base. This Hoogsteen base pair is stacked upon the sixth base pair of the B-type double-helical stem. The second base of the loop is folded into the minor groove, whereas the third base of the loop is partly stacked on the first and fourth bases. The phosphate backbone exhibits a sharp turn between the third and fourth nucleotides of the loop. The peculiar structure of this hairpin loop is discussed in relation to loop folding in DNA and RNA hairpins and in relation to a general model for loop folding.Loop structures in RNA and DNA hairpins have been the subject of numerous studies. We have been interested in these structures because they may serve as models for the folding which occurs in RNA and DNA molecules in the cell, and also because they may provide insight into the mechanism underlying the folding. Our initial studies were concerned with the hairpin fo...

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“…A DNA hairpin is made up of two parts: a base-paired stem and a single-stranded loop connecting the two halves of the stem. Structural studies have shown that the loop of fully complementary hairpins generally adopts a 2-or 4-unpaired-nucleotide structure, due to the tremendous steric constraints imposed by the bonding of the last two nucleotides (29,35,36). A DNA hairpin has therefore to be seen as a dynamic equilibrium adopting the more favorable energy conformation under a given steric stress.…”

Section: Discussionmentioning

confidence: 99%

Nucleotide Deletion and P Addition in V(D)J Recombination: a Determinant Role of the Coding-End Sequence†

Nadel

Feeney

1997

Molecular and Cellular Biology

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During V(D)J recombination, the coding ends to be joined are extensively modified. Those modifications, termed coding-end processing, consist of removal and addition of various numbers of nucleotides. We previously showed in vivo that coding-end processing is specific for each coding end, suggesting that specific motifs in a coding-end sequence influence nucleotide deletion and P-region formation. In this study, we created a panel of recombination substrates containing actual immunoglobulin and T-cell receptor coding-end sequences and dissected the role of each motif by comparing its processing pattern with those of variants containing minimal nucleotide changes from the original sequence. Our results demonstrate the determinant role of specific sequence motifs on coding-end processing and also the importance of the context in which they are found. We show that minimal nucleotide changes in key positions of a coding-end sequence can result in dramatic changes in the processing pattern. We propose that each coding-end sequence dictates a unique hairpin structure, the result of a particular energy conformation between nucleotides organizing the loop and the stem, and that the interplay between this structure and specific sequence motifs influences the frequency and location of nicks which open the coding-end hairpin. These findings indicate that the sequences of the coding ends determine their own processing and have a profound impact on the development of the primary B-and T-cell repertoires.The large repertoire of immunoglobulin (Ig) and T-cell receptor (TCR) variable regions is generated during V(D)J recombination by two main sources of diversity (34). Combinatorial diversity derives from the assembly of one of the many variable (V), diversity (D), and joining (J) gene segments to form a V(D)J exon and, subsequently, from the pairing of the two chains of the heterodimeric receptor. Junctional diversity is created by extensive nucleotide modification at the junctions during the assembly of the gene segments. V(D)J recombination is therefore the earliest mechanism generating diversity in the primary B-and T-cell repertoires.The proper rearrangement of the various gene segments requires the presence of recombination signal sequences (RSS) adjacent to each coding segment. This signal consists of conserved heptamer and nonamer sequences separated by a nonconserved spacer region of 12 or 23 bp (called 12-bp RSS and 23-bp RSS, respectively) (1, 12). The initial DNA break is performed by the RAG1-RAG2 complex, which binds to the RSS and makes a single-strand cut at the 5Ј end of the heptamer at the precise border of the coding end and the RSS (23). The phosphodiester bond of the complementary strand opposite to the initial nick is then attacked by direct transesterification, resulting in a covalently sealed hairpin coding end and a blunt signal end.To proceed through the recombination process, the DNA hairpins formed by the coding ends have to be resolved into free ends, which is presumably done by double-or singlestra...

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Hairpin structures in DNA containing arabinofuranosylcytosine. A combination of nuclear magnetic resonance and molecular dynamics

Cited by 53 publications

References 51 publications

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

The three‐dimensional structure of a DNA hairpin in solution

Nucleotide Deletion and P Addition in V(D)J Recombination: a Determinant Role of the Coding-End Sequence†

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Hairpin structures in DNA containing arabinofuranosylcytosine. A combination of nuclear magnetic resonance and molecular dynamics

Cited by 53 publications

References 51 publications

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H,

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H,

The three‐dimensional structure of a DNA hairpin in solution

Nucleotide Deletion and P Addition in V(D)J Recombination: a Determinant Role of the Coding-End Sequence†

Contact Info

Product

Resources

About

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,