The nucleic acids and their role in the living being

The structure of nucleic acids. The studying of molecular-genetic life organization is connected with the studying of structure and functions of nucleic acids. Nucleic acids are macromolecules. They were firstly discovered by F. Miescher in 1869. However, scientists began to pay attention to the nucleic acids as a place of hereditary information storage only after J. Watson and F. Crick’s works (1953). Nucleic acid exists in two forms: desoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

DNA - is the storage of genetic information. It is in the nucleus chromosomes, in the mitochondria, in the chloroplasts of eukaiyotic cells, in prokaryotic cells, in many viruses. RNA serves for transmitting and realization of hereditary information in prokaryotic and eukaryotic cells. In many viruses RNA work as a primary storage of hereditary information.

Nucleic acids are composed from nucleotide subunits. The nucleotide subunit is composed of tree elements: an organic base, a phosphate group, a 5-carbon sugar. The base is bound to first carbon atom in the sugar and phosphate group is bound to fifth carbon atom in the sugar. Third atom of sugar always has a hydroxyl (-OH) group.

The nucleotide linkage in the nucleic acid molecule is provided by phosphodiester bond between phosphate group of one nucleotide and hydroxyl group of another. Further linking can occur in the same way, since two-unit polymer still has a free 5' - phosphate group at one end and a free 3 - hydroxyl group at the other.

This linking occurs with help of polymerase enzyme. The new nucleotide can be attached to the chain only to 3' hydroxyl group of the polymer. A nucleotide without phosphate group has a name nucleoside. Organic bases are purine - adenine and guanine or pyrimidine - thymine, cytosine and uracil. DNA consists of 2x10*9 and more nucleotides. (Pic 2.1)

Analyzing DNA of different origin, E. Chargaff in 1949-1955 concluded principles of DNA composition. Chargaff results are commonly referred to as Chargaff rules:

1. The proportion of A always equals that of T and C similarly equal to G; A=T, G=C.

2. From the above rule, it follows that there is always an equal proportion of purines (A and G) and pyrimidines (C and T).

3. The number of bases with 6-aminogroupes equal to 6-ketogroupes (A+C=G+T).

4. The ratio of such bases as A+T/G+C is species-specific value.

Pic 2.1. The Structure of nucleic acids: a - nucleotide structure, b- nucleotide linkage to polymer chain, c- scheme of DNA molecule structure, (by V.N. Yarygrn, 1997)

These findings served as a key for DNA structures discovery. J. Watson, F. Crick made a 3-dimenitional model of DNA in form of double helix. (Pic 2.2)

Pic 2.2 The J. Watson and F. Crick DNA model: a - scheme of double helix, b - tree-dimenitional model of DNA

This allowed them to explain physical, chemical and biological properties of DNA. With help of x-ray analysis, it was shown that diameter DNA helix is 2 nm, and made a complete spiral turn every 3.4 nanometers. Each complete spiral turn include 10 nucleotide pairs. The main principles of DNA structure was formulated in following statements:

1. Each DNA molecule consists of two long antiparallel polynucleotide chains, making double helix. The antiparallelity of polynucleotide chains is provided by linkage of 5' end of one chain to 3' end of the other and overwise.

2. Each nucleoside is in the plane, which has a right angle with helix axis.

3. Two chains are bounded to each other with help of hydrogen bonds between bases.

4. The pair’s linkage is very specific. There is only two possible pair A:T and G:C.

5. The sequence of pairs in one chain may vary in wide range but the sequence of pairs in the second chain has to be complementary to it. Thus, the pair sequence in one chain defines the complementary sequence in the other chain.

For discovering DNA dimenitional model J. Watson, F. Crick and M. Wilkins received a Nobel Prize in 1962.

In the DNA, structure it can be distinguished a primary structure - a poly nucleotide chain, a secondary structure - two complementary to each other antiparallel polynucleotide chains, bounded by hydrogen bonds, and third structure - tree dimenitional spiral with characteristics described above. (Pic 2.2)

A DNA molecule is able to double (replication). This is a very complicated process. First, the double stranded DNA molecule separates at one end with help of heliase enzyme. Each strand becomes a matrix for new complementary strand synthesis. As result of this, from one DNA strand appear two, with the same structure. (Pic 2.3)

Pic. 2.3. The DNA molecule replication (N. Green et al., 1990)

The regions of DNA despiralizing by heliase enzyme are called replication forks. At these regions, with help DNA polymerase enzyme DNA of two new molecules is synthesized. During a replication process, the replication fork moves along mother spiral. The DNA fragment from the point of replication start to the point of replication end forms a replication unit - a replicon.

The eukaryotic cells have a large number of replicons. That’s how the replication of DNA of eukaryotic chromosomes starts at several points. In the different replicons, replication may occur at the different or same time. The ability of DNA polymerase to add nucleotides only in direction from 3' to 5' means that the process of replication in two DNA strands should be different.

On a one matrix, the replication of DNA occurs continuously from 3' end to 5' end. On another matrix, the process of replication performed by short fragments. Then the short fragment of DNA are added to the growing chain in the 3' to 5' direction DNA polymerase jumps ahead to fill in another gap. These fragments are called an Okazaki fragments.

Three types of DNA replication can be distinguished: conservative, semiconservative, dispersive. All these types allow making a daughter DNA consisting of the same amount of mother DNA and newly formed. Only distribution of mother DNA in the molecules is different. After conservative replication, the half of daughter DNA molecules is made from new material and second from old one. After semiconservative and dispersive replication, each of daughter DNA molecules has a half made from new material and a half from old one.

However, the semiconservative and dispersive replication can be distinguished after daughter molecules replication. If it is a semiconservative replication 50% of daughter molecules of second generation will be made from half of new material and half of old material. The other 50% will be made from only new material. If it is dispersive replication, all molecules of second generation will be made from 25% of old material and 75% will be made from new material.

The RNA molecule is single strand. It is consist of such nucleotides as adenine, guanine, cytosine and uracil instead of thymine. While helix like folding some complementary regions can bind to each other making spiral. There are exist three RNA types: matrix RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA).

All types of RNA (except viruses RNA) are made on DNA matrix by transcription. Firstly, a long precursor is made than it subject to processing. The more short RNA is made after processing. The primary transcript and intermediate products of RNA synthesis are known as pro-RNA. It became shorter with help of cutting end sequences and some of fragments from the middle of chain. Then rest of the fragments is subject to splicing, that means its binding. Also a new terminal sequences are bounded and some of nucleotides are subject to methylation and hydroxylization.