DNA: Double Helical Structure and Polymorphism

DNA: Double Helical Structure

There had been no other biomolecule that had caught the interest of so many scientists as the DNA molecule. Linus Pauling had figured out the Helical structure common to many fibrous proteins by the early 1950s and was applying his knowledge to the structure of DNA. At the same time, Maurice Wilkins and Rosaling Franklin were employing X-ray crystallography to solve the same problem. Meanwhile, James Watson and Francis Crick started developing scale models of polynucleotides using all the chemical and physical data they could get their hands on. They were in touch with Wilkins regularly and had access to X-ray diffraction data to test their models against. 

The data obtained strongly suggested a helical structure with regularity, at the spacing of 0.34 nm along its axis. They also realized the significance of some evidence published by Erwin Charaff called the Base Pairing Rule, concerning the ratio of the different bases found in DNA. According to this rule, the Purines always equal the pyrimidines in DNA.

DNA Helix Structure

Watson and Crick were experimenting with the concept that DNA could include

1. Two Helical chains of polynucleotides kept united by base pairing between adjacent chains.

2. Hydrogen bonds are discovered to link the base pairs united.

3. Watson and Crick discovered that DNA is made up of 2 strands of polynucleotides. Each chain coils around the other to form a Double Helix, and the 2 chains form a right-handed helical spiral.

4. The chains are antiparallel, with the 3′ 5′ end of one being opposite the 5′ end of the other.

5. Each chain comprises a sugar-phosphate backbone, with bases that project at right angles across the double helix and hydrogen bond with the bases of the opposite chain.

6. Two Purines and two pyrimidines would be too large and too little to bridge the gap between the chains.

7. The Pairings are 0.34 nm apart along the molecule’s axis, accounting for the regularity exhibited by X-ray diffraction.

 DNA polymorphism: A, B and Z DNA

DNA is a dynamic structure that can take on several shapes. Watson and Crick’s discovery of the Double-Helical structure of DNA had a huge impact on biology since it immediately identified how genetic information is stored and copied. The following are the key features of their model:

1. A right-handed Double Helix is formed when two Polynucleotide chains moving in opposite directions coil around a common axis.

2. On the inside of the helix, the purines and pyrimidine bases are located, while the Phosphate and Deoxyribose units are located on the outside.

3. Adenine (A) and guanine (G) are coupled with thymine (T) and cytosine (C). Two perfectly directed hydrogen connections reinforce A—T base pairs, while three such bonds reinforce G—C base pairings.

B-DNA  

The model given by Watson and crick is known as B-DNA Helix. Watson and Crick’s model was based on X-ray Diffraction patterns of DNA fibres, which provide information about the Double Helix’s characteristics that are averaged over its constituent residues. X-ray investigations of DNA crystals can reveal a lot more structural information. However, such research would have to wait until procedures for producing vast quantities of DNA oligomers with specific base sequences were developed. DNA has far more structural polymorphism and diversity than previously thought, according to atomic resolution X-ray examinations of these crystals.

In each monomer, a DNA chain can rotate about six bonds. the glycosidic bond between the base and sugar, the sugar’s C4 — C5 bond, and four bonds in the phosphodiester bridges connecting C3 of one sugar to C5 of the next, compared to only two for polypeptide chains.

One feature of the B—DNA helix is noteworthy. The helix can be smoothly curved into an arc or supercoiled with only minor structural changes. This flexibility is crucial biologically because it allows circular DNA to be produced and DNA to be wrapped around proteins. The ability of DNA to be compacted into a much smaller volume is determined by its deformability. DNA would not fit into a cell if it were forced to be linear.

1. DNA that is bent at distinct locations can also be kinked. Kinking can be caused by certain base sequences, such as a run of at least four adenine residues, or by a protein binding, as will be seen momentarily.

2. The major groove (12 Angstron wide) and minor groove (12 Angstron wide) are two types of grooves found in B-DNA

3. The main groove is slightly deeper than the minor groove (8.5 versus 7.5 Angstron). N-3 is represented by n, O-2 is represented by o, and amino group hydrogen is represented by h in the minor groove.

4. In the minor groove, there is no (AT) on (TA), nho (GC) and ohn (CG) as patterns of donors and acceptors. N – 7 guanine and adenine, as well as O – 4 thymine and O – 6 guanine, are all possible acceptors in the main groove.

5. The major groove displays the patterns nho (AT), ohn (TA), noh (GC), and hon (CG), where n signifies N – 7 and o denotes O – 4 O—6.

A – DNA   

When the relative humidity is lowered below roughly 75%, X-ray diffraction examinations of dehydrated DNA fibres showed a new form dubbed A – DNA.

1. A—DNA is a right-handed Double Helix made up of antiparallel strands kept together by Watson—Crick base pairing, similar to B—DNA.

2. The A Helix is longer and wider than the B helix, and its base pairs are bent instead of parallel to the helix axis.

3. The puckering of their ribose units causes a lot of the structural distinctions between them. C3 is out of the plane formed by the other four atoms of the furanose ring in A – DNA, while C2 is out of the plane in B – DNA. Furthermore, the minor groove almost vanishes.

4. The A Helix’s phosphate groups bind fewer H2O molecules than the phosphates in B –DNA. As a result, dehydration favours the A-type. Furthermore, the minor groove almost vanishes.

5. The A Helix’s phosphate groups bind fewer H2O molecules than the phosphates in B –DNA. As a result, dehydration favours the A-type.

Z-DNA

Z-DNA is a left-handed Double Helix with zigzagging backbone phosphates. Alexander Rich and his colleagues found a new form of DNA helix. When they figured out how to make CGCGCG. The phosphates in the backbone zigzagged, leading to the name Z—DNA. The zigzagging is caused by the fact that the repeating units are dinucleotides rather than mononucleotides. Z—DNA also varies from A and B variants in that it only has one deep helical groove. Short oligonucleotides with alternating pyrimidines and purines adopt the Z—DNA form.

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