Alternative DNA Conformations

While the vast majority of the DNA exists in the canonical B-DNA form, DNA can adopt an amazing array of alternative structures. This is the result of certain particular sequence arrangements of DNA and, in many cases, energy in the DNA double helix from DNA supercoiling, the property of DNA in which the double helix, in a high-energy state, becomes twisted around itself. Some alternative DNA conformations identified are shown in Figure 4.

Unwound DNA. Since A.T base pairs contain two hydrogen bonds and OG base pairs contain three, A+T-rich tracts are less thermally stable that C+G-rich tracts in DNA. Under denaturing conditions (heat or alkali), the DNA begins to "melt" (separate), and unwound regions of DNA will form, and it is the A+T-rich sequences that melt first. In addition, in the presence of superhelical energy (a high-energy state of DNA resulting from its supercoiling, which is the natural form of DNA in the chromosomes of most organisms), A+ T-rich regions can unwind and remain unwound under conditions normally found in the cell. Such sites often provide places for DNA replication proteins to enter DNA to begin the process of chromosome duplication.

Cruciform Structures. DNA sequences are said to be palindromic when they contain inverted repeat symmetry, as in the sequence GGAATT-AATTCC, reading from the 5' to the 3' end. Palindromic sequences can form intramolecular bonds (within a single strand), rather than the normal intermolecular (between the two complementary strands), hydrogen bonds. To form cruciforms ("cross-shaped"), the DNA must form a small unwound structure, and then base pairs must begin to form within each individual strand, thus forming the four-stranded cruciform structure.

Slipped-Strand DNA. Slipped-strand DNA structures can form within direct repeat DNA sequences, such as (CTG)n.(CAG)n and (CGG)n.(CCG)n (where "n" denotes a variable number of repetitions). They form following denaturation, after the strands become unwound, and during renaturation, when the strands come back together. To form slipped-strand DNA, the opposite strands come together in an out-of-alignment fashion, during renaturation. Expansion of such triplet repeats are features of certain neurological diseases.

Intermolecular Triplex DNA. Three-stranded, or triplex DNA, can form within tracts of polypurine.polypyrimidine sequence, such as (GAA)n.(TTC)n. Purines, with their two-ring structures, have the potential to form hydrogen bonds with a second base, even while base paired in the canonical A.T and G.C configurations. This second type of base pair is called a Hoog-steen base pair, and it can form in the major groove (the top of the base pair representations in Figure 2). Pyrimidines can only pair with a single other base, and thus a long Pu.Py tract must be present for triplex DNA formation. The important factor for triplex DNA formation is the presence of an extended purine tract in a single DNA strand. The third-strand base-pairing code is as follows: A can pair with A or T; G can pair with a protonated C (C+) or G.

OOOQC

Figure 4. DNA can exist in a variety of conformations. "Canonical" DNA is the most common, but each of the other forms have particular functions or are found in certain conditions.

Intramolecular Triplex DNA. When a PuPy tract exists that has mirror repeat symmetry (5' GAAGAG-GAGAAG 3'), an intramolecular triplex can form, in which half of the PuPy tract unwinds and one strand wraps into the major groove, forming a triplex. The structure in Figure 4 shows the pyrimidine strand (CTT) pairing with the purine strand (GAA) of a canonical DNA duplex. In an intramolecular triplex, one strand of the unwound region remains unpaired, as shown.

Quadruplex DNA. DNA sequences containing runs of G-C base pairs can form quadruplex, or four-stranded DNA, in which the four DNA strands are held together by Hoogsteen hydrogen bonds between all four guanines. The four guanines are aligned in a plane, and the successive rings of gua-nines are stacked one upon another.

Left-handed Z-DNA. Alternating runs of (CG)n.(CG)n or (TG)n.(CA)n di-nucleotides in DNA, under superhelical tension or high salt (more than 3 M NaCl) (M, moles per liter) can adopt a left-handed helix called Z-DNA. In this form, the two DNA strands become wrapped in a left-handed helix, which is the opposite sense to that of canonical B-DNA. This can occur

Figure 4. DNA can exist in a variety of conformations. "Canonical" DNA is the most common, but each of the other forms have particular functions or are found in certain conditions.

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