Dental Biochemistry 1- (10)

DNA: Structure and replication

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Protein Biosynthesis

The DNA is transcribed to mRNA which is translated into protein with the help of ribosomes.

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Nucleotides • Nucleotides are precursors of the nucleic

acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).

• The nucleic acids are concerned with the storage and transfer of genetic information.

• The universal currency of energy, namely ATP, is a nucleotide derivative.

• Nucleotides are also components of important coenzymes like NAD+ and FAD, and metabolic regulators such as cAMP and cGMP.

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Composition of nucleotides

A nucleotide is made up of three components:

1. Nitrogenous base, (a purine or a pyrimidine).

2. Pentose sugar, either ribose or deoxyribose.

3. Phosphate groups esterified to the sugar 4

• Nucleoside: Formed when a base combines with a pentose sugar.

• Nucleotide: Formed when nucleoside is esterified to phosphate group. It also called nucleoside monophosphate.

• The nucleic acids (DNA and RNA) are polymers of nucleoside monophosphates (nucleotide).

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Bases present in the nucleic acids

1- Purine bases: • The purine bases present in RNA and DNA are the

same; adenine and guanine.

• Uric acid is formed as the end product of the catabolism of other purine bases.

• 2- Pyrimidine bases • The pyrimidine bases present in nucleic acids

are cytosine, thymine and uracil.

• Cytosine is present in both DNA and RNA.

• Thymine is present in DNA and uracil in RNA.

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Nucleoside structure

• Base + Sugar → Nucleoside

• Ribonucleosides: Adenine + Ribose → Adenosine

Guanine + Ribose → Guanosine

Uracil + Ribose → Uradine

Cytosine + Ribose → Cytidine

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• Deoxy ribonucleosides:

Adenine + Deoxyribose → Deoxyadenosine

(d-adenosine)

Guanine + Deoxyribose → d-Guanosine

Cytosine + Deoxyribose → d-Cytidine

Thymine + Deoxyribose → d-thymidine

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Nucleotide structure

• Base + Sugar + Phosphate

• Types of nucleotide:

1- Nucleoside monophosphate

e.g. Adenosine + Pi → Adenosine monophosphate (Adenylic acid ) (AMP).

2- Nucleoside diphosphate

e.g. Adenosine + 2Pi → Adenosine diphosphate (ADP).

3- Nucleoside triphosphate

e.g. Adenosine + 3Pi → Adenosine triphosphate (ATP).

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Nucleotide structure

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AMP

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Structure of DNA • Deoxyribonucleic acid (DNA) is composed of four

deoxyribonucleotides:

Deoxyadenylate (A) - Deoxyguanylate (G)

Deoxycytidylate (C) - Deoxythymidylate (T)

• These units are combined through 3’ to 5’ phosphodiester bonds to polymerize into a long chain.

• The nucleotide is formed by a combination of base + sugar + phosphoric acid.

• The 3’-hydroxyl of one sugar is combined to the 5’-hydroxyl of another sugar through a phosphate group.

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Polynucleotide

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• In the DNA, the base sequence is of paramount importance.

• The genetic information is coded in the specific sequence of bases; if the base is altered, the information is also altered.

• The deoxyribose and phosphodiester linkages are the same in all the repeating nucleotides.

• Therefore, the message will be conveyed, even if the base sequences alone are mentioned as e.g.

5’P-Thymine-Cytosine-Adenine-3’OH

or 5’-T-C-A-3’.

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Watson-Crick model of DNA structure

1. Right handed double helix: • DNA consists of two polydeoxy ribonucleotide

chains twisted around one another in a right handed double helix similar to a spiral staircase.

• The sugar and phosphate groups comprise the handrail and the bases jutting inside represent the steps of the staircase. The bases are located perpendicular to the helix axis, whereas sugars are nearly at right angles to the axis.

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2- The base pairing rule: • Always the two strands are complementary to each

other.

• So, the adenine of one strand will pair with thymine of the opposite strand, while guanine will pair with cytosine.

• The base pairing (A with T; G with C) is called Chargaff’s rule, which states that the number of purines is equal to the number ofpyrimidines.

3- Hydrogen bonding: • The DNA strands are held together mainly by hydrogen

bonds between the purine and pyrimidine bases.

• There are two hydrogen bonds between A and T while there are three hydrogen bonds between C and G.

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4- Antiparallel: • The two strands in a DNA molecule run antiparallel,

which means that one strand runs in the 5’ to 3’ direction, while the other is in the 3’ to 5’ direction.

• This is similar to a road divided into two, each half carrying traffic in the opposite direction.

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Replication of DNA

• During cell division, each daughter cell gets an exact copy of the genetic information of the mother cell.

• This process of copying the DNA is known as DNA replication.

• In the daughter cell, one strand I derived from the mother cell; while the other strand is newly synthesized.

• This is called semi-conservative type of DNA replication. 24

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Steps of Replication

1. Each strand serves as a template or mold, over which a new complementary strand is synthesized.

2. The base pairing rule is always maintained. The new strand is joined to the old strand by hydrogen bonds between base pairs (A with T and G with C).

3. Polymerization of the new strand of DNA is taking place from 5’ to 3’ direction. This means that the template is read in the 3’ to 5’ direction. So, the 3’ end of the last nucleotide is free. 26

4. Thus, two double strands are produced. One double strand goes to one daughter nuclei, and the other to the second daughter nuclei.

• But each daughter cell gets only one strand of the parent DNA molecule.

• Old DNA strand is not degraded, but is conserved for the daughter cell, hence this is semi-conservative synthesis.

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5. DNA polymerase (DNAP).

This enzyme synthesizes a new complementary strand of DNA

6. Initiation of DNA replication.

The DNA replication starts with the recognition of the site of origin of replication.

7. RNA primer is required for DNA synthesis.

An RNA primer, about 100·200 nucleotides long, is synthesized by the RNA primase.

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8. Elongation of DNA strand.

Under the influence of DNA polymerase, nucleotides

and the one continuously polymerized as they are sequentially added. The DNA polymerase carries out the sequential addition of each nucleotide complementary to the one in the template strand

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Steps of Replication

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Inhibitors of DNA replication

• anti-bacterial agents:

Certain compounds will inhibit bacterial enzymes, but will not affect human cells.

• anti-cancer agents:

Some other components will inhibit human enzymes, they will arrest new DNA synthesis, and arrest the cell division.

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