Nucleic acids DNA and RNA are made up of nucleotides which consist of a 5-carbon sugar (deoxyribose in DNA and ribose in RNA), a phosphate group, and a nitrogenous base. DNA contains the bases adenine, guanine, cytosine, and thymine and is located in the cell nucleus, while RNA contains adenine, guanine, cytosine, and uracil and is found throughout the cell. Nucleic acids store and transmit genetic information through their sequence of nucleotides and are essential for all known life.

2. Deoxyribonucleotide
Ribonucleotide

3. Nucleic Acids: DNA and RNA
• Nucleic acids are polymeric macromolecules (High molecular weight) or
large biological macmolecules, essential for all known forms of life.
• Nucleic acids, which include DNA (deoxyribonucleic acid) and RNA (ribonucleic
acid), are made from monomers known as nucleotides.
• Each nucleotide has three components: a 5-carbon sugar, a phosphate group, and
a nitrogenous base. If the sugar is deoxyribose, the polymer is DNA. If the sugar
is ribose, the polymer is RNA.
They are responsible for 2 fundamental properties:
1) Their ability to reproduce their kind or transfer genetic information
2) To undergo mutation
-Nucleic acids are found in all living cells and viruses.
- Friedrich Miescher in 1869 isolated what he called nuclein from the nuclei of pus
cells. Nuclein was shown to have acidic properties, hence it became called nucleic
acid

4. • Together with proteins, nucleic acids are the most important biological
macromolecules; each is found in abundance in all living things,
• Where they function in encoding, transmitting and expressing genetic
information.
• In other words, information is conveyed through the nucleic acid sequence, or
• The order of nucleotides within a DNA or RNA molecule.
• Strings of nucleotides strung together in a specific sequence are the
mechanism for storing and transmitting hereditary,
OR genetic, information via protein synthesis.

5. • In Eukaryotic cells, DNA occurs in combination with proteins called
nucleoproteins chiefly histones of several types.
• Histones are small, highly basic proteins (known amino acid sequence)
• Genes of eukaryotes are present in chromatin which is made up of
protein and DNA along with some RNA.
• Chromatin contains about equal amounts (by weight) of DNA and
protein.
• Prokaryote (unicellular) with single chromosome without true nucleus.
• Nuclear material scattered in cytoplasm, nucleoproteins found in
cytoplasm associated particularly with ribosome where RNA is
ultimately concerned with protein synthesis.

6. The nucleus contains the cell’s DNA (genome) RNA is synthesized
in the nucleus and exported to the cytoplasm
Nucleus
Cytoplasm
DNA
RNA (mRNA)
Proteins
replication
transcription
translation

7. Importance of Nucleic acids
1) Nucleic acids are large molecules that carry tons of small details: all
the genetic information. Nucleic acids are found in every living
thing — plants, animals, bacteria, viruses, fungi — that uses and
converts energy. Every single living thing has something in
common.
2) DNA is carrier of genetic information in all organisms with few exceptions
e.g. Tobacco mosaic virus, poliovirus, influenza virus and some
bacteriophages use RNA for this purpose.
3) Nucleic acids direct synthesis of proteins including enzymes.
4) Mutations are essential for evolution of new varieties and species.
5) All plant viruses have RNA while bacterial and animal viruses have either
DNA or RNA e.g Human immunodeficiency virus (HIV) and
poliomyelitis are RNA viruses while vaccinia and Herpes are DNA
viruses.

8. 6) Cancer research involves extensive studies of nucleic acids.
7) Diseases like Gout and Orotic-aciduria are inborn errors of purine and
pyrimidine metabolism respectively.
8) It is possible to find out defective genes leading to serious diseases
even before birth.
9) It is possible to synthesize genes and incorporate into genome of
selected host cells.
10) Genomic maps and libraries have been prepared.
11) DNA from blood, seminal fluid can be analyzed by which parentage
and involvement of crimes like murder or raps can be detected
with great precision. This is called DNA finger-printing.
12) Gene therapy for certain genetic diseases in human beings is being
studied.

9. 9
Historical Summary of the Discovery of DNA
By the 1950s, it was clear that DNA was the genetic material. The key
scientists who discovered and reported the structure of DNA were:
Linus Pauling 1901-1994 Robert Corey (1897-1971) Rosalind Franklin 1920-1958
Maurice Wilkins 1916- James Watson 1928- Francis Crick 1916-2004

10. DNA secondary structure – double helix
James Watson and Francis Crick, 1953- proposed a model for DNA structure
•DNA is the molecule of heredity (O.Avery, 1944)
•X-ray diffraction (R.Franklin and M. Wilkins)
•E. Chargaff (1940s) G = C and A = T in DNA
Francis Crick Jim Watson

11. Watson-Crick model of DNA was based on X-ray diffraction picture of DNA
fibres (Rosalind Franklin and Maurice Wilkins)
Rosalind Franklin

12. Functions/Biochemical role of Nucleotides
• Enter in structure of ATP
• Form building blocks (Units) of Nucleic Acids (DNA & RNA)
• Enter in structure of coenzymes (NAD, NADP, FMN, FAD: Hydrogen
carriers), acid carrier (Coenzyme-A), methyl donor (S-adenosyl methionine).
• Enter in structure of cyclic AMP (cAMP, cGMP): 2nd messenger
• Nucleoside 5'-triphosphates are carriers of energy.
• Bases serve as recognition units.
• Cyclic nucleotides are signal molecules and regulators of cellular metabolism
and reproduction.
• ATP is central to energy metabolism.
• GTP drives protein synthesis.
• CTP drives lipid synthesis.
• UTP drives carbohydrate metabolism.

13. Nucleotide Function
– Energetic Intermediates
– Adenine Enzyme Cofactors
– Regulatory Molecules

14. Nucleotides

15. Phospho-Anhydrides and Phosphate
Esters – High Energy Bonds

16. Co-Enzyme A – Carrier for
Acetyl units in intermediary
metabolism, fatty acid synthesis
and oxidation

17. NAD+/NADH, NADP+/NADPH
and FAD/FADH2
• Redox Cofactors

18. Regulatory/Signalling Molecules

19. Nucleic Acids
DNA RNA
Central Dogma of Biology
DNA RNA Proteins Cellular Action
transcription translation
DNA
replication (deoxyribonucleic acids) (ribonucleic acids)

20. Two types of nucleic acid are found:
• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)
 DNA is found in the nucleus with small amounts in mitochondria and
chloroplasts
 RNA is found throughout the cell
 Nucleic acids are polynucleotides
 Their building blocks are nucleotides

21. DNA as genetic material: The circumstantial evidence
1. Present in all cells and virtually restricted to the nucleus
2. The amount of DNA in somatic cells (body cells) of any given species is
constant (like the number of chromosomes)
3. The DNA content of gametes (sex cells) is half that of somatic cells.
In cases of polyploidy (multiple sets of chromosomes), the DNA content
increases by a proportional factor
4. The mutagenic effect of UV light peaks at 253.7nm. The peak for the
absorption of UV light by DNA

22. DNA contains two kinds of information:
• The base sequences of genes that encode the amino acid sequences
of proteins and the nucleotide sequences of functional RNA (rRNA
and tRNA).
• The gene regulatory networks that control the expression of protein-
encoding (and functional RNA-encoding) genes.

23. NUCLEOTIDE STRUCTURE
PHOSPATE SUGAR
Ribose or
Deoxyribose
NUCLEOTIDE
BASE
PURINES PYRIMIDINES
Adenine (A)
Guanine(G)
Cytocine (C)
Thymine (T)
Uracil (U)

24. Garrett and Grisham, Biochemistry, Third Edition
(a) The pyrimidine ring system; by convention, atoms are numbered as indicated. (b) The
purine ring system, atoms numbered as shown.

25. Sugar “Pucker”

26. The Building Blocks of DNA
-O
O
H(OH)
HH
HH
O
OP
O
O-
Purine or
Pyrimidine
Base
Phosphate
Pentose sugar
Nucleoside
Nucleotide
1'
2'3'
4'
5'
-N-glycosidic bond

27. Building Blocks
– Nucleotides = Base + Sugar + Phosphate
– Nucleosides = Base + Sugar
– Nitrogen Bases
• Purines (5 + 6 membered rings) – numbering
– Adenine Guanine
• Pyrimidines (6 membered ring) – numbering
– ThymineCytosine Uracil
– Pentose Sugars (numbering)
• – Ribose
• – Deoxy Ribose

28. DNA and RNA nucleobases
N
N
N
N
H
NH2
N
NH
NN
H
O
NH2
N
N
H
NH2
O
H3C
NH
N
H
O
O
Guanine (G)Adenine (A)
Thymine (T)Cytosine (C)
NH
N
H
O
O
Uracil (U)
N
N
NN
H
Purine
N
N
H
Pyrimidine
1
2
3
4
5
6
3
2
1
6
4
5
7
8
9
(DNA only) (RNA only)

29. Purine Nucleotides

30. Pyrimidine Nucleotides

31. nucleobase (Deoxy)
nucleoside
5’-mononucleotide
Adenine (A)
Guanine (G)
Thymine (T)
Cytosine (C)
Uracil (U)
2’-Deoxyadenosine
(dA)
2’- Deoxyguanosine
(dG)
2’- Deoxythymidine
(dT)
2’- Deoxycytidine
(dC)
Uridine (U)
Deoxyadenosine 5’-monophosphate
(5’-dAMP)
Deoxyguanosine 5’-monophosphate
(5’-dGMP)
Deoxythymidine 5’-monophosphate
(5’-dTMP)
Deoxycytidine 5’-monophosphate
(5’-dCMP)
Uridine 5’-monophosphate (5’-UMP)
Nomenclature of Nucleobases, Nucleosides and Mononucleotides

32. Structural differences between DNA and RNA
H3C
NH
N
H
O
O
Thymine (T)
NH
N
H
O
O
Uracil (U)
DNA RNA
O
H
HH
H
CH2
H
O
HO
Base
2'-deoxyribose
O
OH
HH
CH2
H
O
HO
Base
ribose
H

33. Preferred conformations of nucleobases and sugars in
DNA and RNA
HO
O
OH
N
N
NH2
O
Anti conformation
HO
O
OH
N
N
NH2
O
Syn conformation
HO
O
H (OH)
HO
BASE
HO
O
H (OH)
HO
BASE
2' endo (B-DNA)
1'
3' endo (RNA)
3'
1'
3'
2' 5'5'
7.0 A
5.9 A
Sugar puckers:

34. Nucleosides must be converted to 5’-Triphosphates to be part of DNA and RNA
HO
O
OH
O
O
OH
P
HO
HO
O
O
O
OH
P
O
P
O
HO
HO
O
OH
Base Base
Base
O
O
OH
P
O
P
O
O
OH
Base
OH
OP
O
HO
HO
Kinas e
Kinas e
Kinas e
Monophosphate
DiphosphateTriphosphate
ATP
ATP
ATP

35. 35
Structure of Nucleic Acids
• Polymers of four nucleotides
• Linked by alternating sugar-phosphate bonds
• RNA: ribose and A, G, C, U
• DNA: deoxyribose and A,G,C,T
nucleotide nucleotide nucleotide nucleotide
P sugar
base
P sugar
base
P sugar
base
P sugar
base

36. Phosphodiester bonds
– Formed by Polymerase and Ligase activities
– C-5' OH carries the phosphate in nucleotides
– C5' - O - P - O - C3'
– Phosphate pKa ~ 0
– Natural Oligonucleotides have 5‘-P and 3‘-0H
– Base hydrolysis due to ionizaiton of 2' OH in RNA

37. The Structure of DNA
An antiparallel double helix
• Diameter of 2 nm
• Circular in prokaryotic cells.
• Length of 1.6 million nm (E. coli)
• Compact and folded (E. coli cell is only 2000 nm long)
• The linear eukaryotic DNA is wrapped around histone proteins to
form nucleosomes.
• Base pairs: A-T, G-C

38. DNA is arranged 5’ to 3’
Connected by Phosphates
Linking in DNA biopolymer: DNA primary structure

40. Oligonucleotide naming / drawing
conventions
– 5’ - Left to Right - 3’
– pACGTOH
– ACGT

42. A, B and Z DNA
• A form – favored by RNA
• B form – Standard DNA
double helix under
physiological conditions
• Z form – laboratory
anomaly,
– Left Handed
– Requires Alt. GC
– High Salt/ Charge
neutralization
A, B & Z DNA Kinemages

43. •Polymers linked 3' to 5' by phosphodiester bridges.
•Sequence is always read 5' to 3'.
• In terms of genetic information, this corresponds to "N to C" in
proteins.
• The base sequence of a nucleic acid is its distinctive characteristic.
• pGpApCpU, GpApCpUp, pGpApCpUp, GACU, dGACT

44. Types of Nucleic acids
• DNA - one type, one purpose:
- a single DNA molecules in virus and bacteria
- Eukaryotic cells have many diploid chromosomes mainly in nucleus,
but also mitochondria and chloroplasts.
• RNA - 3 (or 4) types, 3 (or 4) purposes
– ribosomal RNA - the basis of structure and function of ribosomes
– messenger RNA - carries the message
– transfer RNA - carries the amino acids
– Small nuclear RNA
– Small non-coding RNAs

46. DNA
Backbone
Flexibility
• Multiple
Degrees of
Rotational
Freedom

47. Semi-
conservative
Replication

48. RNA: Typically single stranded: Produced during transcription
• mRNA: Carries information encoded in genes to direct protein synthesis on ribosomes
– Derive from heterogeneous nuclear RNA (hnRNA)
– RNA processed by splicing (removal of introns and joining of exons), capping (5’ end),
and polyA tail addition (3’ end)
• rRNA: Components of ribosome: Protein synthesis
– Small subunit of ribosome: Single rRNA
– Large subunit of ribosome: Large subunit rRNA, 5S rRNA, and in eukaryotes 5.8S
rRNA
• tRNA: Carriers of activated amino acids used by ribosome for protein synthesis
• snRNA: Small nuclear RNAs (Important in converting hnRNA to mature mRNA)
• siRNAs: Small interfering RNAs: Degrade mRNAs (post-transcriptional gene silencing)
• miRNAs: micro RNAs: Bind to mRNA and block translation
• snoRNAs: Small nucleolar RNAs: Required for certain RNA modification

49. Messenger RNAs
• Contain protein coding information
– ATG start codon to UAA, UAG, UGA Stop Codon
– A cistron is the unit of RNA that encodes one polypeptide chain
– Prokaryotic mRNAs are poly-cistronic
– Eukaryotic mRNAs are mono-cistronic
• Base pairing/3D structure is the exception
– Can be used to regulate RNA stability termination, RNA editng, RNA
splicing

50. Distinctive Base composition foretell base
pairing patterns
– Hydrolysis of DNA and analysis of base
composition
• Same for different individuals of a given species
• Same over time
• Same in different tissues
• %A = %T and %G = %C (Chargaff's Rules)
– Amino acid compositions vary under all three
conditions
– No quantitative relationships in AA composition

51. Telomeres
Telomeres are sequences at the end of eukaryotic chromosomes that
help stabilize the chromosome. Telomeres are repeats of the
following sequence:
5’-(TxGy)n x and y = 1 to 4
3’-(AxCy)n The TG strand is longer
5’-TTTGGTTTGGTTTGGTTTGGTTTGGTTTGG…
3’-AAACCAAACCAAACC…
Can be >10,000 nucleotides in mammals. The ends of the
chromosome are replicated by the enzyme telomerase.