The influence of exocyclic substituents of purine bases on DNA curvature.

Diekmann, Stephan; Kitzing, Eberhard Von; McLaughlin, Larry W.; Ott, Johann; Eckstein, Fritz

doi:10.1073/pnas.84.23.8257

Cited by 57 publications

(55 citation statements)

References 42 publications

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“…This observation indicates that the cleavage pattern of a particular sequence can be significantly affected by the substitution of only a few nucleotides. This last observation is consistent with previous work (Diekmann et al 1987;Koo and Crothers 1987), which demonstrated that single nucleotides substituted for adenine in the center of an A-tract sequence could completely abolish the curvature of that DNA molecule, therefore drastically changing the overall shape and structure as the result of a modest change in sequence.…”

Section: Degeneracy Of Hydroxyl Radical Cleavage Data Patternssupporting

confidence: 81%

Construction of a genome-scale structural map at single-nucleotide resolution

Greenbaum¹,

Pang²,

Tullius³

2007

Genome Res.

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Few methods are available for mapping the local structure of DNA throughout a genome. The hydroxyl radical cleavage pattern is a measure of the local variation in solvent-accessible surface area of duplex DNA, and thus provides information on the local shape and structure of DNA. We report the construction of a relational database, ORChID (OH Radical Cleavage Intensity Database), that contains extensive hydroxyl radical cleavage data produced from two DNA libraries. We have used the ORChID database to develop a set of algorithms that are capable of predicting the hydroxyl radical cleavage pattern of a DNA sequence of essentially any length, to high accuracy. We have used the prediction algorithm to produce a structural map of the 30 Mb of the ENCODE regions of the human genome.[Supplemental material is available online at www.genome.org.]While the linear sequence of nucleotides is the level at which most interpretations of a genome are made, a new appreciation of the effect of local DNA structure on genome function is emerging. Much effort has gone into the derivation of general rules regarding the effect of the sequence of DNA on its structure. High-resolution X-ray and NMR structures have clearly revealed the variability of DNA structure (Dickerson and Drew 1981;Calladine 1982;Calladine and Drew 1986;Yanagi et al. 1991;Dickerson 1992Dickerson , 1997Grzeskowiak 1996;Olson et al. 1998;Ng and Dickerson 2001;Barbic et al. 2003;Hays et al. 2005), and have shown that the conformation of a nucleotide residue is dependent at least on its nearest neighbors, and possibly more (Dickerson and Drew 1981;Dickerson 1983;Calladine and Drew 1986;Nelson et al. 1987;Bhattacharyya and Bansal 1990;DiGabriele and Steitz 1993;El Hassan and Calladine 1997;Johansson et al. 2000; Packer et al. 2000a,b;Gardiner et al. 2003). Although much knowledge has been gained from the study of DNA crystal structures, high-resolution structure determinations are resourceintensive and are applicable only to moderate-sized DNA molecules. In order to comprehensively sample the structure of all possible DNA sequences in an unbiased manner, alternative methods are necessary.We report here the construction of a library of hydroxyl radical cleavage patterns of DNA, as a means of compiling structural information for a wide variety of DNA sequences. Although the hydroxyl radical cleavage pattern (Price and Tullius 1992) does not yield a high-resolution three-dimensional structure of a DNA molecule, it is a reflection of an important structural parameter, the solvent-accessible surface area of the DNA backbone (Balasubramanian et al. 1998). The cleavage pattern thus provides an image of the shape of the DNA backbone and how it varies with respect to nucleotide sequence. We describe the use of a fluorescence-based sequencer to obtain cleavage patterns, and introduce methods for normalization and quantitation of cleavage data. We present the design considerations of a relational database, ORChID (OH Radical Cleavage Intensity Database), to hold hydroxyl radical...

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Section: Degeneracy Of Hydroxyl Radical Cleavage Data Patternssupporting

confidence: 81%

Construction of a genome-scale structural map at single-nucleotide resolution

Greenbaum¹,

Pang²,

Tullius³

2007

Genome Res.

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“…My NMR results also correlate well with gel electrophoresis studies which measured the extent of DNA bending in oligomers containing the site AAAAA:TTTTT, where variants were made containing one or more I»C substitutions (Diekmann et al, 1987;Koo & Crothers, 1987). (Pelton, 1990).…”

Section: Basesupporting

confidence: 54%

NMR studies of DNA oligomers and their interactions with minor groove binding ligands

Fagan

1996

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Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. I studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity 1 of the reactive agent. The DNA cleaving agent netropsin-diazene binds at the predicted DNA site, but the presence of the diazene reduces the affinity and the orientational preference of the ligand compared to distamycin. A tethered ligand containing a 2,3-bis(hydroxymethyl) pyrrole crosslinked to a DNA duplex exhibits many similarities to mitomycin C:DNA complexes. The tether unexpectedly bridges one base pair. These results are important considerations in ligand design, since sometimes ligand binding behavior cannot be predicted from the behavior of the parent molecule.The pairing geometry of cytosine with the highly mutagenic base analog 2-aminopurine has been debated for years. With the use of NMR spectroscopy and selectively 15 N-labeled DNA, the AP«C mispair was found to form a wobble geometry.The structure and stability of this base mispair depend upon the local base sequence.Approved: ., ( -,"_,,,

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“…The exocyclic groups of DNA would be expected to affect the mechanics of bending in two ways. First, their presence could exercise constraints on the compressibility of both the major and the minor grooves (27), more especially at extreme, protein-induced deformations. Second, addition or loss of the purine 2-amino group, by altering the number of hydrogen bonds in a base pair, also will affect the rotational freedom of the substituted bases about the long axis of the base FIG.…”

Section: Discussionmentioning

confidence: 99%

“…We observe that nucleosomal particles assembled with I-, UI-, and IM-substituted DNAs all possess high amplitudes of hydroxylradical cleavage modulation. In addition, these same DNA species are characterized by an increased apparent intrinsic curvature, possibly because of the stacking of an I-C or I-M base pair on adjacent A-T pairs, thus creating the structural equivalent of a short dA:dT tract (27,(32)(33)(34). Indeed, recent crystal structures have shown that single I-C base pairs sandwiched between A-T pairs in the sequence AIA exhibit the high propeller twist normally characteristic of A-T but not G-C base pairs (32).…”

Section: Fig 4 Exocyclic Groups Affect the Rotational Positioning Omentioning

confidence: 99%

The exocyclic groups of DNA modulate the affinity and positioning of the histone octamer

Buttinelli

Minnock²,

Panetta³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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To investigate the nature of the chemical determinants in DNA required for nonspecific binding and bending by proteins we have created a novel DNA in which inosine-5-methylcytosine and 2,6-diaminopurine-uracil base pairs are substituted for normal base pairs in a defined DNA sequence. This procedure completely switches the patterns of the base pair H bonding and attachment of exocyclic groups. We show that this DNA binds a histone octamer more tightly than normal DNA but, surprisingly, does not alter the orientation of the sequence on the surface of the protein. However, in general, the addition or removal of DNA exocyclic groups reduces or increases, respectively, the affinity for the histone octamer. The average incremental change in binding energy for a single exocyclic group is Ϸ40 J͞mol. The orientation of the DNA in core nucleosomes also is sensitive to the number and nature of the exocyclic groups present. Notably, substitutionwiththenaturallyoccurringcytosineanalogue,5-methylcytosine, shifts the preferred rotational position by 3 bp, whereas incorporating 2,6-diaminopurine shifts it 2 bp in the opposite direction. These manipulations potentially would alter the accessibility of a protein recognition sequence on the surface of the histone octamer. We propose that exocyclic groups impose steric constraints on protein-induced DNA wrapping and are also important in determining the orientation of DNA on a protein surface. In addition, we consider the implications of the selection of A-T and G-C base pairs in natural DNA.The local deformation of DNA by DNA-bending proteins can substantially exceed the normal conformational fluctuations of DNA free in solution. Although the interactions that determine the local sequence-dependent conformation of free DNA are relatively well understood (1-7), the nature of the chemical constraints that limit its further deformation have not been explored extensively. The nucleosome core particle in which the central 125 bp of DNA are wrapped in 1.6 superhelical turns about the histone octamer (8, 9) provides a good system to study this problem. In this particle both the major and minor grooves are compressed on the inside of the wrapped DNA and widened on the outside. A major determinant of the rotational placement of the DNA in the nucleosome is the periodic occurrence of short A͞T-rich sequences in helical phase and of short G͞C-rich sequences in the opposite phase. These short sequences favor local conformations with narrow and wide minor grooves, respectively, and thus together facilitate the tight wrapping of DNA (10-16).To investigate the nature of other chemical determinants that constrain the wrapping of DNA around the histone octamer we chose a prokaryotic DNA sequence derived from the Escherichia coli tyrT promoter. Previous studies have shown that the histone octamer occupies a preferred rotational position on this DNA (10). We modified this DNA by replacing the naturally occurring bases with analogues either lacking or containing additional exocyclic groups b...

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The influence of exocyclic substituents of purine bases on DNA curvature.

Abstract: Complementary oligonucleotides with 5' overhanging deoxyguanosine or deoxycytidine stretches, re-

Cited by 57 publications

References 42 publications

Construction of a genome-scale structural map at single-nucleotide resolution

Construction of a genome-scale structural map at single-nucleotide resolution

NMR studies of DNA oligomers and their interactions with minor groove binding ligands

The exocyclic groups of DNA modulate the affinity and positioning of the histone octamer

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