NUCLEIC ACIDS. DNA. RNA.

Nucleic Acids The name nucleic acids comes from the fact that they are isolated from nuclear material. Although they were discovered a long time ago (in 1868 by Friedrich Misher), it was later in the 40s of the twentieth century, that their chemical composition was discovered. Evidence was proved that these are the molecules, through which the cell program of protein synthesis cells it is hereditary to the subsequent generation of cells and is thus called hereditary or genetic program or information. Essence
M

Nucleic Acids are high molecular organic compounds, composed by high number of linear arranged nucleotides. The hereditary information in the organism is due to them. The nucleotides consist of bound monosaccharide, nitrogen base (N-base) and phosphate acid residues (H3PO4). The cell uses one and the same chemical compound for different functions. One of the most important functions of nucleotides is to serve as building blocks of nucleic acids. Nucleotides are composed of 2 types of monosaccharides made of 5Carbon atoms ribose or deoxyribose. (DNA deoxyribose, RNA ribose). One of the monosaccharide C-atoms is linked to the phosphate group (5-C sugar) and another one is bound to the nitrogen base. There are 2 types of N-bases contained in nucleotides small and large ones. The small bases are thymine (T), uracil (U) and cytosine (C) and the large ones are adenine (A) and guanine (G).

Thymine (T) Uracil (U) Cytosine (C) Adenine (A) Guanine (G)

C5H6N2O2 C4H4N2O2 C4H5N3O C5H5N5 C5H5N5O Types

5-methyluracil 2,4-pyrimidinediol 4-amino-1H-pyrimidine-2one 6-aminopurine 2-amino-6-hydroxypurine

Nucleic acids are the polymers of nucleotides. When nucleotides are bound, water is released the way it is released during polymerization of proteins and a polynucleotide chain is formed. They exist in two forms deoxyribonucleic (DNA) and ribonucleic acid (RNA). In DNA the monosaccharide residue is deoxyribose, while in RNA it is ribose (this is what the names of the two biopolymers are derived from). The nitrogen bases of DNA are adenine, guanine, cytosine and thymine. The ones in RNA are adenine, guanine, cytosine and thymine The sugar-phosphate backbone of nucleic acids is formed by the monosaccharide residues and the phosphate groups. The nitrogen bases extend outwardly from the backbone. One end of a polynucleotide chain always has a free phosphate (P-) group and the other a free

hydroxyl (OH-) group. Nucleic acids have a definite direction of synthesis. The phosphate group is always considered the beginning of the polynucleotide chain and the hydroxyl group the end. The direction of a polynucleotide chain is very important for the proper interpreting of the information encoded in DNA. This information has meaning only if it is read in the right direction. The presence of phosphate groups gives nucleic acids acidic properties and negative charges. This fact explains why nucleic acids easily combine with proteins, which contain positive charges predominantly. DNA

In the year 1953 one of the most important discoveries in biology was made James D. Watson and Francis Crick discovered the structure of DNA. This was an exciting discovery not only because an important chemical formula was deciphered, but also because it led to a significant consequence the sequence of bases along the DNA chain, is what the genetic information is encoded in. Structure of DNA

DNA was discovered to be a double molecule. In DNA two polynucleotide strands form a double helix. The two polynucleotide strands are linked by non-covalent bonds only and have opposite directions. It is the double spiral of the DNA structure in which all the hereditary program of every living cell is encoded. A distinctive characteristic of the double helix is that when it is formed one large base is always connected with a small base from the opposite chain: the base adenine is bound to thymine and the base guanine to cytosine. Thus, a specific complementarity is kept. The N-bases of the nucleotides are directed inwards from the sugar-phosphate backbone of the chains as if hidden into the molecule. The bases of the opposite polynucleotide chains are connected by weak hydrogen bonds. A large molecule, such as DNA, has a large number of hydrogen bonds that, even though weak, provide stability to the spiral. Only a stable molecule can keep the hereditary information of the cell. The formation of the double helix is always accomplished through hydrogen bonds established between a large base of one polynucleotide chain and a small one belonging to the opposite polynucleotide chain: adenine to thymine and cytosine to guanine. This is the only way a spiral, in which the distance between the polynucleotide chains is the same throughout the chains length, could be formed. Such interaction between the bases is possible because of their complementarity. The requirement of complementarity between A (a large base) and T (a small base) and between G (large base) and C (a small base) determines the way a new exact copy of the DNA will be synthesized.

10

Types of DNA DNA can either be a linear or a ring (cyclic) structure, where its both ends are bound together.
M

DNA molecules are stable but also changeable molecules in both structural and chemical aspects. Only this combination of stability and a certain degree of changeability will ensure the fulfillment of their complex biological functions. Under certain conditions in a solution (high temperature, high acidity or alkaline pH), the double helix of DNA is disrupted and the molecule is denatured. This process is often called melting. DNA main hereditary molecule The main biological function of DNA is the preservation and transfer of the cell program. The DNA molecule contains all the information required for the existence of a cell. The cell program is the information about the complete biological characteristics of the cell, its structural and functional traits.

11

For each amino acid residue in a polypeptide chain there is a corresponding sequence of three nucleotides in one of the DNA strands. The nucleotide triplet in a DNA molecule corresponding to an amino acid is called genetic code. The genetic code is the set of 20 amino acids in proteins. The genetic code has three digits and through it the cell reads and observes the information contained in DNA. In order to understand the meaning of the words in the language of the nucleotides, they have to be read in a certain direction. If the reading had no direction, the cell would be unable to get accurate instructions for the synthesis of proteins.

12

The portion of DNA that carries information for the synthesis of a polypeptide chain (a 13 protein) is called gene. The gene is the smallest hereditary functional unit. Are you a living creature? Than congratulations! You have DNA! That microscopic little building block of life that makes us all the same, but grants is with distinct differences. But facts to help you better understand the little bit of genetic coding that makes you, you! REPLICATION One of the most intricate anabolic processes in the cell is DNA biosynthesis (replication). This process is of extreme importance because it ensures the preservation of the hereditary information and its passing on to subsequent generations of cells during cell division. This is why replication is considered both a typical biochemical and genetic process. During DNA synthesis, the two polynucleotide strands are separated and each of them serves as a template, to which a new complementary nucleotide strand will attach.
14 15 16

K M K

17

The process, in which the DNA of the cell is doubled, is called replication or biosynthesis of DNA. Nucleotides + DNA-template
M Enzymes

DNA
17

Like any anabolic process, replication requires energy. It is provided by the initial molecules themselves. These nucleotides contain deoxyribose, bound to three instead of one phosphate residues. They have chemical bonds, rich in energy. When they are bound, two phosphate residues and energy, used in the synthesis of the polynucleotide strand of DNA, are discharged. DNA synthesis occurs only when the cell is about to divide and the cell program has to be passed on to the daughter cells unchanged. Prior to every cell division DNA is doubled. This process occurs at very high speed and accuracy. The whole DNA of human cell is replicated in 8 hours while bacterial DNA is doubled in 30 min.

18

By replication two new molecules of DNA are formed, each of them containing one old polynucleotide strand and one new polynucleotide strand. The process has a definite direction. 19 The synthesis of the polynucleotide strand always begins from the end that has a free phosphate group P and is directed to the end with the hydroxyl group OH-. DNA polymerase the basic enzyme of replication This Enzyme has the ability to attach nucleotides to the free end of the growing polynucleotide strand. DNA polymerase is very sensitive to errors. It is able to remove any error nucleotide it comes across during DNA synthesis. Besides having polymerizing activity and ability to remove error nucleotides, DNA polymerase also has the ability to fill in gaps with missing nucleotides. However, along with all these enzyme activities, we must also mention the fact that DNA polymerase is unable to begin the process of DNA synthesis by itself, but can only continue it. Naturally, the question which enzyme gives start to the synthesis of the polynucleotide strand arises. The beginning of the synthesis is marked by production of small segments of RNA. DNA polymerase consecutively adds nucleotides to the small segments of RNA; then it removes the RNA fragment and fills in the gaps with nucleotide for DNA. DNA Replication begins at a certain point, called origin of replication. The origin is a specific nucleotide sequence, something achieved with the aid of a special enzyme catalyzing the procedure. The complex of enzymes and proteins that participate in DNA biosynthesis is called protein complex of replication.
Replication Video

20

STRUCTURE OF RNA
M

RNA molecules are long and unbranched. They are also made of nucleotides, however, instead of deoxyribose, they contain the monosaccharide ribose and instead of the N-base 21 thymine (T) the N-base uracil (U). Similarly to DNA, RNA has the ability to bond to different proteins and thus form compounds with different functions. If the chemical formulae of ribose and deoxyribose are examined carefully, one will notice that in the ribose molecule linked to the second carbon there is a OH group instead of an H atom. This at first sight insignificant difference is the reason why RNA shows greater chemical instability than DNA and greater reactivity as well. In water solution, RNA is broken into parts much more easily than DNA. Double spiral sections of RNA The spatial structure of RNA is quite different from that of DNA. The molecules of RNA are single stranded. Portions of the polynucleotide may wind and form double spiral sections. Like in DNA, the formation is carried out between complementary bases, never belonging to different strands though, but ones that belong to different portions of one and the same nucleotide strand. In RNA such complementary bases are A to U and G to C. The existence of such double strand portions allows for remote nucleotides in the linear structure to come closer to one another just like amino acid residues from the polypeptide chain get closer as it is folded and a more complex structure is formed. The complex spatial arrangement parts of the molecules of some RNA molecules have, forms a structure that resembles an active enzyme site. That is why some RNA molecules show catalytic activity. This is an important characteristic of RNA, in which it rather resembles proteins (than DNA). If we compare the three biopolymers DNA, RNA and proteins, we will find out that RNA is more stable than proteins but less stable than DNA. On the other hand, it is more reactive than DNA but less reactive than proteins.

22

23

In terms of spatial arrangement and functional activity, RNA takes an intermediate place 24 between DNA and proteins. Types of RNA Three types of RNA, present in every cell, are recognized: messenger, transfer and ribosomal. The messenger RNA molecules (mRNA) make up to 2% of the cells RNA. Their name is derived from their function namely carrying the script for the synthesis of proteins. As on a magnetic tape, the script for the synthesis of cell proteins is converted from DNA nucleotide 25 sequence into RNA nucleotide sequence. Each mRNA carries the script for the synthesis of one and sometime of several polypeptide chains. In the molecule of RNA, each triplet of nucleotides that corresponds to a certain amino acid in a peptide chain is called a codon.

Transfer RNA molecules (tRNA) are small molecules with a very specific structure they resemble a cloverleaf. The molecule is additionally folded and it then resembles the letter L. tRNA-s contain linear as well as double spiral sections. The name of the tRNA-s comes from the function the molecule fulfills. tRNA-s read the script carried by the mRNA and thus determine the place of each amino acid molecule in the synthesized protein molecule. Each tRNA has two specific sections in its molecule. One section recognizes the codon for a certain amino acid in mRNA, the other section binds to an amino acid. The section that recognizes the codon of mRNA is called anticodon.
M 25

The anticodon consists of three nucleotides that are complementary to the nucleotides of the codon. Thus following the rule of complementarity, the anticodon of tRNA finds the exact codon on the mRNA. The third type of RNA is ribosomal RNA (rRNA). Its molecules make up about 80% of the cell RNA. rRNA forms compounds with proteins and builds up the ribosomes (cell organelles). tRNA transports the amino acids from the cytoplasm to the ribosomes where it arranges them in the sequence determined by the script of mRNA. The ribosomes bind the arranged amino acids by means of peptide bonds. Thus, a new polypeptide chain (a protein molecule) is synthesized. CENTRAL DOGMA OF BIOLOGY During RNA synthesis in the nucleus, the information residing in the form of triplets of nucleotides to the DNA is copied. This information is transferred out of the nucleus into the cytoplasm where the ribosomes are found. There it is decoded and according to it cell proteins are synthesized.

26

The flow of information in the cell has one definite direction from the nucleic acids to the proteins: DNA -> RNA -> protein. This statement is designated as the central dogma of modern biology. A lot of new discoveries showed that DNA and RNA synthesis require protein enzymes and other protein factors. Therefore, proteins are not only products of decoding the information but also active participants in this process. TRANSCTIPTION All types of RNA are synthesized according to a template principle, through copying of segments (genes) of one of the DNA strands a process is called transcription. The enzyme RNA-polymerase uses the active forms of the ribonucleotides as substrates and can independently carry out the synthesis. The enzyme recognizes a certain section of DNA, from which RNA synthesis begins, and continues the formation of the strand through the consecutive addition of nucleotides. Most RNAs are synthesized in the form of inactive precursor molecules. The chemical changes, which these molecules undergo, make them active and able to perform their biological function. Such processes are reorganized as maturation.
Transcription Video

27

TRANSLATION The synthesis of proteins or translation is a process, during which the transcribed genetic information is translated from the language of nucleotide to the language of amino acids. It takes place in the cytosol according to a template principle, has a definite direction, and is performed with the help of ribosomes. Translation is performed in three stages: beginning, elongation and termination of the synthesis of the polynucleotide chain. At the 28 beginning, a complex is formed from the ribosome, mRNA, and tRNA, carrying the first amino acid. The complex has two spaces for two loaded tRNA-s. initially the first two tRNAs occupy the 2 sites and the first peptide bond is formed with the combination of the first two amino acids, carried by the two tRNA-s. During elongation stage, the subsequent amino acids are continually added and the polypeptide chain grows. The synthesis stops when the ribosome reaches a stop codon. Translation is a complex process, in which enzymes and others proteins take part.
Translation Video