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Dental Biochemistry 1- (10)


    DNA: Structure and replication




1
Protein Biosynthesis
The DNA is transcribed to
 mRNA which is translated into
 protein with the help of
 ribosomes.

2
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.
  3
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
4
   sugar
• 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).




  5
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.
  6
7
Nucleoside structure
• Base + Sugar           → Nucleoside


• Ribonucleosides:
      Adenine       +   Ribose   →   Adenosine
      Guanine       +   Ribose   →   Guanosine
      Uracil        +   Ribose   →   Uradine
      Cytosine      +   Ribose   →   Cytidine


  8
• Deoxy ribonucleosides:

Adenine + Deoxyribose → Deoxyadenosine
                          (d-adenosine)
Guanine + Deoxyribose → d-Guanosine
Cytosine + Deoxyribose → d-Cytidine
Thymine + Deoxyribose → d-thymidine



9
10
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).
  11
Nucleotide structure




12
AMP




13
14
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.
  15
Polynucleotide




16
17
• 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’.
  18
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.

  19
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.
   20
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.




   21
22
23
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
25
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.
  27
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.
  28
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




  29
Steps of Replication




30
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.

  31

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Lec 10 level 3-de (dna structure and replication)

  • 1. Dental Biochemistry 1- (10) DNA: Structure and replication 1
  • 2. Protein Biosynthesis The DNA is transcribed to mRNA which is translated into protein with the help of ribosomes. 2
  • 3. 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. 3
  • 4. 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 4 sugar
  • 5. • 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). 5
  • 6. 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. 6
  • 7. 7
  • 8. Nucleoside structure • Base + Sugar → Nucleoside • Ribonucleosides: Adenine + Ribose → Adenosine Guanine + Ribose → Guanosine Uracil + Ribose → Uradine Cytosine + Ribose → Cytidine 8
  • 9. • Deoxy ribonucleosides: Adenine + Deoxyribose → Deoxyadenosine (d-adenosine) Guanine + Deoxyribose → d-Guanosine Cytosine + Deoxyribose → d-Cytidine Thymine + Deoxyribose → d-thymidine 9
  • 10. 10
  • 11. 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). 11
  • 14. 14
  • 15. 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. 15
  • 17. 17
  • 18. • 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’. 18
  • 19. 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. 19
  • 20. 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. 20
  • 21. 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. 21
  • 22. 22
  • 23. 23
  • 24. 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
  • 25. 25
  • 26. 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
  • 27. 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. 27
  • 28. 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. 28
  • 29. 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 29
  • 31. 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. 31