Helical DNA

The distribution is determined by the small number of counts present in the residuals to the single-riistance fit. 

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Section 28 9 Within the cell nucleus double helical DNA adopts a supercoiled terti ary structure m which short sections are wound around proteins called histones This reduces the effective length of the DNA and maintains it m an ordered arrangement... 

Replication fork (Sechon 28 9) Point at which strands of double helical DNA separate... 

A related method is the component synthesis method [17], which uses a so-called static condition to model the interactions between parts of a molecule whose corresponding diagonal blocks in the Hessian are first diagonalized. It has been combined with a residue clustering algorithm that provides a hierarchy of parts, which at the lowest level provides small enough matrices for efficient diagonalization [18]. It has been applied to double-helical DNA [17] and the protein crambin [18]. 

Dimerization of the Ce-zinc cluster transcription factors involves an a-helical coiled coil in the dimerization region. Coiled coils, often called leucine zippers, are also found in a large group of transcription factors that do not contain zinc. The leucine zipper is made up of two a helices in a coiled coil with every seventh residue leucine or some other large hydrophobic residue, such as isoleucine or valine. Leucine zipper transcription factors (b/zip) include factors characterized by heterodimerization, for example Fos and Jun. The a-helical DNA-binding motifs of the heterodimers recognize quite different base sequences and are continous with the a helices of the zipper. 

Helix-loop-helix (b/HLH) transcription factors are either heterodimers or homodimers with basic a-helical DNA-binding regions that lie across the major groove, rather than along it, and these helices extend into the four-helix bundle that forms the dimerization region. A modification of the b/HLH structure is seen in some transcription factors (b/HLH/zip) in which the four-helix bundle extends into a classic leucine zipper. 

Although relatively dehydrated DNA fibers can be shown to adopt the A-conformation under physiological conditions, it is unclear whether DNA ever assumes this form in vivo. However, double-helical DNA RNA hybrids probably have an A-like conformation. The 2 -OH in RNA sterically prevents dou-... 

Coding strand (Section 28.4) The strand of double-helical DNA that contains the gene. 

Mrksich, M., M.E. Parks, and P.B. Dervan. Hairpin peptide motif A new class of oligopeptides for sequence-specific recognition in the minor-groove of double-helical DNA. J. Am. Chem. Soc. 1994, 116, 7983-7988. 

Moser H.E., Dervan P.B. Sequence-specific cleavage of double helical DNA by triple helix formation. Science 1987 238 645-650. 

FIG. 3 Three-dimensional (3D) DNA networks as crystallization matrices for the selective binding of DNA-recognition proteins [8]. The latter, represented by shaded spheres, bind specifically to recognition sites of the six-connected, cubic DNA lattice. For srmphfication, linear double-helical DNA stretches are represented by lines. 

The double-helical DNA is packaged into a more compact structure by a number of proteins, most notably the basic proteins called histones. This condensation may serve a regulatory role and certainly has a practical purpose. The DNA present within the nucleus of a cell, if simply extended, would be about 1 meter long. The chromosomal proteins compact this long strand of DNA so that it can be packaged into a nucleus with a volume of a few cubic micrometers. 

Unlike solid state -stacks, however, double helical DNA is a molecular structure. Here CT processes are considered in terms of electron or hole transfer and transport, rather than in terms of material conductivity. Moreover, the 7r-stack of DNA is constructed of four distinct bases and is therefore heterogeneous and generally non-periodic. This establishes differences in redox energetics and electronic coupling along the w-stack. The intimate association of DNA with the water and counterions of its environment further defines its structure and contributes to inhomogeneity along the mole-... 

Fig. 1 The w-stack of double helical DNA. In this idealized model of B-DNA the stack of heterocyclic aromatic base pairs is distinctly visible within the sugar-phosphate backbone (schematized by ribbons) a view perpendicular to the helical axis b view down the helical axis. It is the stacking of aromatic DNA bases, approximately 3.4 A apart, that imparts the DNA with its unique ability to mediate charge transport. Base stacking interactions, and DNA charge transport, are exquisitely sensitive to the sequence-depen-dent structure and flexibility of DNA...

The reactivity of a series of closely related substances can either be enhanced or inhibited depending on the type and extent of interaction with double-helical DNA. This was shown in a kinetic study of the substitution of ethylenediamine (en) or A-, A- -dimethylethylcncdiamine (Me2en) by thiourea in the palladium(II) complexes [Pd(4,4,-R2bpy)(en)](PF6)2 (R = H or Me), [Pd(en)2](PF6)2, and [Pd(Me2en)2](PF6)2, in water and in the presence of calf thymus DNA.183... 

Fig, 11. Diagrammatic representation of a planar intercalating guest molecule complexed between adjacent base pairs of the double helical DNA host structure. The base pairs and intercalator are represented by stippled rods. Note the increased base pair separation caused by complexation with the guest. 

The four histone groups that are composed of ho-mogeneous proteins, H2A, H2B, H3, and H4, make up the nucleosome core. Each core consists of two copies of the four histones. The double-stranded DNA is wrapped twice around each core in a left-handed superhelix. A superhelix is the name given to the additional helix made by the double-stranded, helical DNA as it is wrapped around the nucleosome core. A familiar superhelix in everyday life is a twisted spiral telephone cord. The nucleosome core of histones do not recognize specific DNA structures rather, they can bind to any stretch of DNA as long as it is not too close to a neighboring nucleosome. The order of contact of histones to the DNA is as follows ... 

In E. coli cells, DNA replication starts at a specific site called oriC. The oriC locus contains only 245 base pairs. Similar sequences are responsible for initiating the synthesis of plasmid and bacteriophage DNA. The oriC nucleotide sequence binds several units of the tetrameric form of the dnaA protein. This protein is named for the gene that encodes it. The dnaB and dnaC proteins then bind to the complex. As a result of binding these proteins, a portion of the helical DNA is unwound. This forces the rest of the DNA into a left-handed double helix that wraps around the proteins to give a structure... 

The structures shown in Fig. 4-1 are for B-form DNA, the usual form of the molecule in solution. Different double-helical DNA structures can be formed by rotating various bonds that connect the structure. These are termed different conformations. The A and B conformations are both right-handed helices that differ in pitch (how much the helix rises per turn) and other molecular properties. Z-DNA is a left-handed helical form of DNA in which the phosphate backbones of the two antiparallel DNA strands are still arranged in a helix but with a more irregular appearance. The conformation of DNA (A, B, or Z) depends on the temperature and salt concentration as well as the base composition of the DNA. Z-DNA appears to be favored in certain regions of DNA in which the sequence is rich in G and C base pairs. 

Fig. 3. X-ray crystal structure of cis- Pt(NH3)2 2--d(CCTCTG G TCTCC) d(GGA GACCAGAGG) showing that the DNA duplex is kinked by ca. 40° toward the major groove and has a juxtaposition of A-like and B-like helical DNA segments (structure reference PDBID, 1AIO). Adapted from (47).

Attempts have been made to prepare carborane-containing DNA binders by adding carborane units to representative DNA intercalators (acridine, ethidium) and a DNA groove binder (distamysine), which have high binding affinity with DNA (Scheme 2.2-8). The intercalators insert themselves into a gap between the base pairs of double-helical DNA [32, 33]. 

Ho et al. were able to verify the a-helical shape of the polymer by circular dichroism (CD) spectra. No structural elements were observed until the formation of the double helical DNA at which point they observed a right-handed a-helix in the polythiophene backbone. Their work demonstrates the power of fluorometric detection as they noted a seven order of magnitude increase in detection sensitivity (20 fM in 200 pi) simply through the use of fluorometric detection as opposed to UV-vis absorption. The polymer in solution has a high fluorescence yield with a maximum at 530 nm (Fig. 11a). Upon formation of the duplex the fluorescence is significantly quenched (Fig. lib), while with the addition of the complementary DNA and triplex formation, the fluorescence intensity is enhanced by a factor of 5 (Fig. 11c). The inherent sensitivity of the spectral shift even allowed distinction between DNA with only one and two mismatched bases (Fig. lOBd, e). 

In a recent paper, Krasnow and co-workers (120) applied a Rec A protein coating to DNA knots and catenanes to enhance visualization of the helical DNA segments and, in particular, to determine the absolute handedness of the knots. The Rec A protein is known to bind cooperatively to duplex DNA, forming a stiffened complex about 100 A in diameter in the presence of ATPase (121). 

D. Porschke and J. Ronnenberg, The reaction of aromatic peptides with a double helical DNA. Quantitative characterization of a two step reaction scheme, Biophys. Chem. 13, 283-290 (1981). 

Fig. 44. Stereo view of the prealbumin dimer. The black triangles are /9 bulges which help to turn outward the /S ribbons that form the loops proposed as a possible site for binding double-helical DNA.

Thuong N, Helene C (1993) Sequence specific recognition and modification of double helical DNA by oligonucleotides. Angew. Chem Int Ed Engl 32 666-690 Tien Kuo M, Hsu TC (1978) Biochemical and cytological studies of bleomycin actions on chromatin and chromosomes. Chromosoma 68(3) 229-240... 

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