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Query: UNIPROT:P06889 (Mol)
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The DNA oligomer of sequence IC-C-G-G has been synthesized, and its X-ray crystal structure solved at a resolution of 2.0 A, using anomalous scattering from iodines in phase analysis: 48 cycles of Jack-Levitt restrained least-squares refinement resulted in a residual error of 19.9% over all data, or 16.5% for two-sigma data. Two double-helical tetramers stack in the crystal to form a continuous octamer, except for the two missing phosphate connections across the center. The octamer has a mean helix rotation of 33.7 degrees (10.7 base-pairs per turn), rise of 2.87 A, mean inclination angle of base-pairs of 14 degrees, and mean base-pair propeller twist of +16.3 degrees. Local variations in both helix rotation and base plane roll angles, including those across the center of the octamer, are as predicted from base sequence by sum functions sigma 1 and sigma 2. The three known DNA octamers: IC-C-G-G/IC-C-G-G, G-G-T-A-T-A-C-C and G-G-C-C-G-G-C-C, make up a graded series in this order, with monotonically changing structural parameters. An exhaustive comparison of torsion angle correlations among the known A helices confirms some structural expectations and reveals some new features. 86 water molecules have been located per double-helical IC-C-G-G tetramer (the asymmetric unit), of which 451/2 per tetramer lie within a first hydrogen-bonded shell of hydration. No ordered water structure is observed comparable to the minor groove spine of hydration in B-DNA.
J Mol Biol 1984 Apr 25
PMID:Helix geometry and hydration in an A-DNA tetramer: IC-C-G-G. 672 97

The crystal structure of the double-helical B-DNA dodecamer of sequence C-G-C-G-A-A-T-T-C-G-C-G has been solved and refined independently in three forms: (1) the parent sequence at room temperature; (2) the same sequence at 16 K; and (3) the 9-bromo variant C-G-C-G-A-A-T-TBrC-G-C-G at 7 degrees C in 60% (v/v) 2-methyl-2,4-pentanediol. The latter two structures show extensive hydration along the phosphate backbone, a feature that was invisible in the native structure because of high temperature factors (indicating thermal or static disorder) of the backbone atoms. Sixty-five solvent peaks are associated with the phosphate backbone, or an average of three per phosphate group. Nineteen other molecules form a first shell of hydration to base edge N and O atoms within the major groove, and 36 more are found in upper hydration layers. The latter tend to occur in strings or clusters spanning the major groove from one phosphate group to another. A single spermine molecule also spans the major groove. In the minor groove, the zig-zag spine of hydration that we believe to be principally responsible for stabilizing the B form of DNA is found in all three structures. Upper level hydration in the minor groove is relatively sparse, and consists mainly of strings of water molecules extending across the groove, with few contacts to the spine below. Sugar O-1' atoms are closely associated with water molecules, but these are chiefly molecules in the spine, so the association may reflect the geometry of the minor groove rather than any intrinsic attraction of O-1' atoms for hydration. The phosphate O-3' and O-5' atoms within the backbone chain are least hydrated of all, although no physical or steric impediment seems to exist that would deny access to these oxygen atoms by water molecules.
J Mol Biol 1983 Jan 05
PMID:Ordered water structure around a B-DNA dodecamer. A quantitative study. 683 28

Adenovirus early region 1A (E1A) is the first transcription unit expressed after infection. It encodes a protein which controls the expression of all other early viral genes. The E1A mRNAs have one major capped 5' terminus which maps 31 nucleotides downstream from a T-A-T-A sequence (C. Baker and E. Ziff. J. Mol. Biol. 149:189-221, 1981). In addition, a minor set of E1A mRNAs are observed during the early phase of infection which have 5' termini mapping at approximately -160, -185, and -230 relative to the major cap site (Osborne et al., Cell 29:139-148, 1982). Here we report the occurrence of another set of minor E1A mRNAs which were observed exclusively after the initiation of viral DNA replication. These late specific E1A mRNAs had cap sites which mapped at approximately -300, -325, -360, and -375 relative to the major cap site. The appearance of these minor late E1A mRNAs was blocked by the DNA synthesis inhibitor cytosine arabinoside. These same late specific E1A mRNAs were synthesized from E1A-containing plasmids which replicate in monkey cells. This demonstrated that neither late specific adenovirus proteins nor adenovirus-specific chromatin structure was required for the production of the late specific E1A mRNAs. Adenovirus mutants in which the E1A T-A-T-A box region had been deleted also synthesized the corresponding deleted forms of the late specific mRNAs after initiation of DNA replication. These results indicate that the process of DNA replication alters the specificity of E1A transcription initiation in a promoter region which is at least 375 nucleotides in length.
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PMID:Far upstream initiation sites for adenovirus early region 1A transcription are utilized after the onset of viral DNA replication. 683 69

The crystal structures of the synthetic self-complementary octamer d(G-G-T-A-T-A-C-C) and its 5-bromouracil-containing analogue have been refined to R values of 20% and 14% at resolutions of 1.8 and 2.25 A, respectively. The molecules adopt and A-DNA type double-helical conformation, which is minimally affected by crystal forces. A detailed analysis of the structure shows a considerable influence of the nucleotide sequence on the base-pair stacking patterns. In particular, the electrostatic stacking interactions between adjacent guanine and thymine bases produce symmetric bending of the double helix and a major-groove widening. The sugar-phosphate backbone appears to be only slightly affected by the base sequence. The local variations in the base-pair orientation are brought about by correlated adjustments in the backbone torsion angles and the glycosidic orientation. Sequence-dependent conformational variations of the type observed here may contribute to the specificity of certain protein-DNA interactions.
J Mol Biol 1983 May 15
PMID:Sequence-dependent conformation of an A-DNA double helix. The crystal structure of the octamer d(G-G-T-A-T-A-C-C). 685 42

Conditions are described for observing by X-ray fibre diffraction the A, B and S conformations of the poly[d(G-C)] . poly[d(G-C)] double-helix and also a new form designated as B". For fibres with an appropriate ionic content, transitions between these conformations can be induced by varying the relative humidity of the fibre environment. With increasing relative humidity the transitions B" leads to A leads to S leads to B occur. However, reducing the relative humidity does not result in a simple reversal of these transitions. If the relative humidity is reduced rapidly, a B leads to A transition is observed followed by an A leads to B" transition, but if it is reduced slowly, the transition is from B to S. Once the S form has been assumed, further reduction in the relative humidity does not result in a transition to the A form. The S form emerges as a particularly stable form of the poly[d(G-C)] . poly[d(G-C)] double-helix. From the point of view of its relationship to the classical A and B forms, the S form of poly[d(G-C)] . poly[d(G-C)] is shown to exhibit similarities to the D form of poly[d(A-T)] . poly[d(A-T)].
J Mol Biol 1983 Aug 25
PMID:Conformational transitions in the synthetic polynucleotide poly[d(G-C)] . poly[d(G-C)] double-helix. 688 55

Molecular mechanics studies have been carried out on "B-DNA-like" structures of [d(C-G-C-G-A-A-T-T-C-G-C-G)](2) and [d(A)](12).[d(T)](12). Each of the backbone torsion angles (psi, phi, omega, omega', phi') has been "forced" to alternative values from the normal B-DNA values (g(+), t, g(-), g(-), t conformations). Compensating torsion angle changes preserve most of the base stacking energy in the double helix. In a second part of the study, one purine N3-pyrimidine N1 distance at a time has been forced to a value of 6 A in an attempt to simulate the base opening motions required to rationalize proton exchange data for DNA. When the 6-A constraint is removed, many of the structures revert to the normal Watson-Crick hydrogen-bonded structure, but a number are trapped in structures approximately 5 kcal/mol higher in energy than the starting B-DNA structure. The relative energy of these structures, some of which involve a non-Watson-Crick thymine C2(carbonyl)[unk]adenine 6NH(2) hydrogen bond, are qualitatively consistent with the DeltaH for a "base pair-open state" suggested by Mandal et al. of 4-6 kcal/mol [Mandal, C., Kallenbach, N. R. & Englander, S. W. (1979) J. Mol. Biol. 135, 391-411]. The picture of DNA flexibility emerging from this study depicts the backbone as undergoing rapid motion between local torsional minima on a nanosecond time scale. Backbone motion is mainly localized within a dinucleoside segment and generally not conformationally coupled along the chain or across the base pairs. Base motions are much smaller in magnitude than backbone motions. Base sliding allows imino N-H exchange, but it is localized, and only a small fraction of the N-H groups is exposed at any one time. Stacking and hydrogen bonding cause a rigid core of bases in the center of the molecule accounting for the hydrodynamic properties of DNA.
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PMID:Molecular mechanical studies of DNA flexibility: coupled backbone torsion angles and base-pair openings. 695 79

Thermodynamic parameters of the process of water phase transition in poly[d(A-T)] solutions in the wide range of polymer concentration have been studied. Curves of the heat capacity changes (delta Cp) depending on concentration of polymer and the temperature in the area of ice-water phase transition have been plotted. Thermodynamic parameters of the process of helix--random coli transition in water solutions of poly[d(A-T)] have been measured. Hydration (n) of poly[d(A-T)]: nAT = 28 mol H2O . mol-1 b. p. has been determined. Comparison of poly[d(A-T)] hydration with hydration of natural DNA shows that the hydration of AT-pairs exceed the amount of water, bound with GC-pairs (nGC congruent to 16--20 mol H2O . mol-1 b. p.). It was concluded that when describing the process of helix-random coil transition in DNA it is necessary to take into account not only the phenomenon of heterogeneity of stacking interactions, but also heterogeneity ("aperiodicity") in the structure of the hydrate shell of DNA molecules.
Mol Biol (Mosk)
PMID:[Investigation of hydration of poly[d(A-T)] polynucleotide in helical and random coli states by the method of low temperature scanning microcalorimetry]. 724 34

Nuclear extracts from maize endosperm were used to investigate protein-DNA interactions in the 5'-upstream region of the Zc1 and Zc2 genes. These genes encode for zeins of apparent molecular mass (MWapp) 16 and 28 kDa, respectively, which accumulate in the endosperm during seed maturation. Binding assays revealed specific binding of a nuclear protein to three A/T-rich elements, 0.9-1.0 kbp upstream from the initiation codon. One of these elements (41 bp, 88% A/T), present in Zc1, contained a 13 nucleotide duplication. The other two (28 bp, 86% A/T; 42 bp alternating A-T) are consecutive elements in Zc2. Competition experiments strongly suggest that the three elements bind to the same protein. Protein-DNA interaction was detected in endosperm nuclear extracts of 8 to 21 days after pollination (DAP), as well as in 25 DAP embryos and in different tissues from plantlets. The protein factor has an MWapp of ca. 30 kDa. This factor has properties suggesting it is an HMG-like protein. These results are consistent with a growing accumulation of data for a number of genes indicating that A/T-rich elements, located at distal and proximal zones of the 5'-flanking sequences, interact with HMG-like proteins.
Plant Mol Biol 1994 Dec
PMID:Narrow A/T-rich zones present at the distal 5'-flanking sequences of the zein genes Zc1 and Zc2 bind a unique 30 kDa HMG-like protein. 785 25

Cells from patients with ataxia-telangiectasia (AT) are more sensitive than cells from normal individuals to a number of compounds which induce DNA damage via oxygen-derived free radical attack. We tested the hypothesis that AT cells would show a sensitivity to reactive oxygen species (ROS) generated by activated inflammatory cells. AT cells were exposed to neutrophils activated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or to xanthine/xanthine oxidase (X/XO), an enzyme system which generates superoxide and hydrogen peroxide. Induced micronuclei (MN) frequencies (corrected for spontaneous MN frequencies) were significantly higher in AT cell cultures than in cultures from normal individuals (comparison of MN frequencies of AT vs. normal cultures: for treatment with activated neutrophils, P = 0.003; for X/XO, P = 0.05). The comet assay was used to determine whether the elevated chromosomal damage in the treated AT cells was due to a difference in strand breakage or its rejoining. X/XO treatment was used in studies of single-stranded (SS) DNA breakage, and X-ray treatment for double-stranded (DS) DNA damage. AT and normal cells showed no significant differences in the initial levels of SS (P = 0.29) or DS (P = 0.91) DNA damage. Likewise, they exhibited similar rejoining kinetics (rejoining half-time for SS = 10 min, for DS = 30 min). These data support the involvement of the AT loci in determining a cell's ability to deal with oxidative stress, although the mechanism underlying this effect has yet to be resolved. The data also suggest that AT patients are at elevated risk of sustaining DNA damage in tissues undergoing inflammatory reactions.
Environ Mol Mutagen 1994
PMID:Response of fibroblast cultures from ataxia-telangiectasia patients to reactive oxygen species generated during inflammatory reactions. 792 23

Mutants of S49 mouse lymphoma cells resistant to cytolysis by analogs of cyclic AMP (cAMP) generally have missense mutations in the gene encoding the regulatory subunit of cAMP-dependent protein kinase. We have compared the mutations in 95 spontaneous isolates with those in 60 mutagen-induced isolates by sequence analysis of amplified cDNAs. Twenty-nine single basepair substitutions in 19 codons produced selectable phenotypes. The spontaneous mutant spectrum was dominated by a CpG transition hotspot in the codon for Arg334. This and other nearby CpG sites were found to be methylated in genomic S49 cell DNA by restriction enzyme analyses. Most of the remaining spontaneous mutants had either G-C-->C-G or T-A-->G-C transversions, which have been associated with damage caused by oxygen radicals. In contrast, the majority of mutants induced with the alkylating mutagens ethyl methanesulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine had G-C-->A-T mutations at non-CpG sites; in addition, EMS induced several A-T-->G-C, A-T-->T-A, and G-C-->T-A substitutions. A single ICR191-induced mutant analyzed had a unique A-T-->G-C lesion. A number of spontaneous and mutagen-induced isolates had closely linked double or triple substitutions, and two isolates had tandem triple substitutions.
Somat Cell Mol Genet 1994 Jul
PMID:Spectrum of spontaneous missense mutations causing cyclic AMP-resistance phenotypes in cultured S49 mouse lymphoma cells differs markedly from those of mutations induced by alkylating mutagens. 797 5


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