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DNA structure

The Watson-Crick base-pairing of the two strands largely determines the secondary

structure of DNA. All naturally occurring DNAs are double-stranded, for at least

some of their lifetimes. Double-stranded DNA is a fairly uniform structure, and theneed for a regular structure is one way in which changes in DNA (genetic mutations)

can be detected. The fact that A-T base pairs and G-C base pairs have very similar

sizes means that no bulges or gaps exist within the double helix. An irregula r

place in the double helix means that something is wrong with the structure, and this

signals the need for DNA repair systems to fix the damage.

The A-T base pair has two hydrogen bonds; each base serves as H-donor for one

bond and as H-acceptor for the other.

The G-C base pair has three hydrogen bonds; G is an acceptor for one for these, anda donor for two. This has important consequences for the thermal melting of

DNAs, which depends on their base composition.

Figure 3

Thermal melting refers to heating a DNA solution until the two strands of DNA

separate, as shown in Figure4. Conversely, a double-stranded molecule can be

formed from complementary single stands.

Melting and helix formation of nucleic acids are often detected by the absorbance

of ultraviolet light. This process can be understood in the following way: The

stacked bases shield each other from light. As a result, the absorbance of UV light

whose wavelength is 260 nanometers (the A260) of a double-helical DNA is less than

that of the same DNA, whose strands are separated (the random coil). This effect is

called the hypochromicity (less-color) of the double-helical DNA.

If a double-stranded DNA is heated, the strands separate. The temperature at which

the DNA is halfway between the double-stranded and the random structure is called

the melting temperature (Tm) of that DNA. The Tm of a DNA depends on base

composition. G-C base pairs are stronger than A-T base pairs; therefore, DNAs with

a high G+C content have a higher Tm than do DNAs with a higher A+T content. For

example, human DNA, which is close to 50 percent G+C, might melt at 70, while

DNA from the bacterium Streptomyces, which has close to 73 percent G+C, might

melt at 85. The Tm of a DNA also depends on solvent composition. High ionicstrengthfor example, a high concentration of NaClpromotes the double-stranded

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state (raises the Tm) of a given DNA because the higher concentration of positive

sodium ions masks the negative charge of the phosphates in the DNA backbone.

Finally, the Tm of a DNA depends on how well its bases match up. A synthetic DNA

double strand made with some mismatched base-pairs has a lower Tm compared to

a completely double-stranded DNA. This last property is important in using DNAfrom one species to detect similar DNA sequences of another species. For example,

the DNA coding for an enzyme from human cells can form double helices with mouse

DNA sequences coding for the same enzyme; however, the mouse-mouse and

human-human double strands will both melt at a higher temperature than will the

human-mouse hybrid DNA double helices.

Figure 4

Direct reactions with DNA serve as the molecular basis for the action of several anti-

tumor drugs. Cancer is primarily a disease of uncontrolled cell growth, and cell

growth depends on DNA synthesis. Cancer cells are often more sensitive than

normal cells to compounds that damage DNA. For example, the anti-tumor drug

cisplatin reacts with guanine bases in DNA and the daunomycin antibiotics act by

inserting into the DNA chain between base pairs. In either case, these biochemical

events can lead to the death of a tumor cell.

DNA tertiary structure

The DNA double helix may be arranged in space, in a tertiary arrangement of the

strands. The two strands of DNA wind around each other. In a covalently closed

circular DNA, this means that the two strands can't be separated. Because the DNA

strands can't be separated, the total number of turns in a given molecule of closedcircular DNA is a constant, called the Linking Number, or Lk. The linking number

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of a DNA is an integer and has two components, the Twist ( Tw), or number of

helical turns of the DNA, and the Writhe ( Wr), or the number of supercoiled

turns in the DNA. Because L is a constant, the relationship can be shown by the

equation:

Figures5aand5b, which show a double helical DNA with a linking number equal to

23, best illustrate this equation.

Normally, this DNA would have a linking number equal to 25, so it is underwound.

The DNA double helical structures in the previous figure have the same value of Lk;

however, the DNA can be supercoiled, with the two underwindings taken up by the

negative supercoils. This is equivalent to two turns'-worth of single-stranded DNA

and no supercoils. This interconversion of helical and superhelical turns is important

in gene transcription and regulation.

Figure 5a

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Figure 5b

Enzymes called DNA topoisomerases alter Lk, the linking number of a DNA, by a

bond breaking and rejoining process. Naturally-occurring DNAs have negative

supercoils; that is, they are underwound.Type I topoisomerases (sometimes

called nicking-closing enzymes) carry out the conversion of negatively supercoiled

DNA to relaxed DNA in increments of one turn. That is, they increase Lk by

increments of one to a final value of zero. Type I topoisomerases are energy

independent, because they don't require ATP for their reactions. Some anti-tumor

drugs, including campothecin, target the eukaryotic topoisomerase I enzyme. Type

II topoisomerases (sometimes called DNA gyrases) reduce Lk by increments of two.

These enzymes are ATP-dependent and will alter the linking number of any closed

circular DNA. The antibiotic naladixic acid, which is used to treat urinary tract

infections, targets the prokaryotic enzyme. Type II topoisomerases act on naturally

occurring DNAs to make them supercoiled. Topoisomerases play an essential role in

DNA replication and transcription.

DNA Structure

The 3 dimensional structure of DNA can be described in terms of primary,secondary, tertiary, and quaternary structure.

The primary structure of DNA is the sequence itself - the order of nucleotides inthe deoxyribonucleic acid polymer.

The sequence alphabet is restricted to only 4 letters (GATC), but these lettersmust contain:

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the code specifying the order of amino acids in proteins the punctuation that controls the beginning and end of protein coding

sequences and the splicing of introns

the regulatory information that specifies when and how much of eachprotein to make in each cell at various developmental stages

instructions for the transcription of RNA molecules that do not encodeprotein (tRNA, ribosomal RNA)

information that controls the replication of the DNA molecule the structural information for the 3-dimensional shape of the DNA molecule

itself.

The secondary structure of DNA is relatively straightforward - it is a doublehelix.

The tertiary and quaternary structure is less well understood.

The double helix is itself supercoiled (with enzymes like DNA gyrase), and it iswrapped around histones.

In addition, there are a wide variety of proteins that form complexes with DNAin order to replicate it, transcribe it into RNA, and regulate the transcriptional

process.

Many, if not all, of these proteins bind to the DNA molecule at specificsequences, so primary sequence determines function.