1.
R.C. Gupta
Professor and Head
Department of Biochemistry
National Institute of Medical Sciences
Jaipur, India
Chemistry of Nucleic Acids
(DNA and RNA)

2.
Nucleic acids are known as information
molecules
They store genetic information
The nucleic acids are of two types:
• Deoxyribonucleic acid (DNA)
• Ribonucleic acid (RNA)

3.
In most of the organisms, genetic
information is present in DNA
In some viruses, it is present in RNA

4.
The information present in DNA concerns
the synthesis of proteins
This information is present in a coded
form
Different types of RNA are required to
synthesize the proteins

5.
The nucleic acids are large polymers
Their building blocks are nucleotides
DNA is a polymer of deoxyribonucleotides
RNA is a polymer of ribonucleotides

6.
DNA is present in the nucleus (in
eukaryotes, some DNA is present in the
mitochondria also)
RNA is mainly extranuclear

7.
Deoxyribonucleic acid (DNA)
Miescher named it as nuclein as it was
present in the nucleus
The earliest evidence about the
presence of DNA in cells was
obtained by Friedrich Miescher in
1869

8.
Richard Altmann found that
nuclein was an acid; hence he
named it as nucleic acid
It 1919, Phoebus Levene
identified the components of
nucleic acid

9.
The components of nucleic acid were
found to be bases, sugars and phosphate
The nucleic acid containing deoxyribose
was named DNA
The nucleic acid containing ribose was
named RNA

10.
The role of DNA as genetic material
was first shown by Griffith in 1928
He conducted his experiments on
pneumococci
Pneumococci are of two types
Encapsulated Non-encapsulated
EMB-RCG

11.
Encapsulated pneumococci form smooth
colonies, and are pathogenic
Non-encapsulated pneumococci form
rough colonies, and are non-pathogenic
Each type produces its own kind of
offspring

12.
Griffith transferred nuclear material from
encapsulated pneumococci into non-
encapsulated pneumococci
When the non-encapsulated pneumococci
divided, the daughter cells had capsules,
and were pathogenic
Thus, it was proved that genetic information
is present in the nucleus

13.
Griffith termed nuclear material as the
transforming principle
However, nuclear material contains a
variety of compounds
Due to their diversity, proteins and nucleic
acids became the prime candidates for
‘transforming principle’

14.
Avery et al (1944) treated nuclear
material with enzymes that
hydrolyse DNA or RNA or proteins
Hydrolysis of DNA destroyed the trans-
forming activity of nuclear matter but
hydrolysis of RNA or proteins did not

15.
Avery et al concluded that genetic
information is present in DNA
Some researchers still speculated that
genetic information might be present in
nuclear proteins and not in DNA
This doubt was cleared by Hershey and
Chase in 1952

16.
Martha Chase Alfred Hershey

17.
Hershey and Chase conducted their
studies on T2 bacteriophage, a DNA virus
T2 bacteriophage is made up of a DNA
core surrounded by a protein coat
T2 bacteriophage infects the bacterium,
E. coli

18.
The bacteriophage multiplies inside the
infected E. coli
When the number of viruses becomes too
large, the bacterial cell ruptures
The viruses are released

19.
The experiment was repeated using 35S
as label
This time, viral proteins were labelled and
the virus was allowed to infect E. coli

20.
This showed that when the virus infected the
bacterium, only the viral DNA entered the
bacterial cell and not the proteins
Since progeny viruses were formed and proteins
surrounded DNA, viral DNA must have directed
the synthesis of new proteins
This established the role of DNA as the genetic
material

21.
Structure of DNA
Chargaff (1950) studied the base
composition of DNA obtained
from diverse sources
He found that number of A
residues was equal to T residues
and number of C residues was
equal to G residues in every DNA
A = T
C = G

22.
Wilkins and Franklin did extensive x-ray
crystallographic studies on DNA
Maurice Wilkins Rosalind Franklin
They showed that DNA has a helical
structure

23.
X-ray crystallographic images of DNA
Typical of helical structure
Typical of helical structure

24.
Watson
Crick
James Watson and Francis
Crick analyzed:
X-ray crystallographic data
And other facts
Structures of purine and
pyrimidine bases
Chargaff’s observations

25.
CcCHARGAFF’S OBSERVATIONS

26.
Size of purines and pyrimidines

27.
Watson & Crick proposed a model of DNA structure

28.
Watson & Crick announced their discovery
on Feb 28, 1953 (published in April, 1953)
Their model was consistent with all the
known features of DNA

29.
Each strand of DNA is a polymer of
mononucleotides
The successive nucleotides in a strand are
linked by 3', 5'-phosphodiester bonds
According to Watson & Crick model, DNA
is a double-stranded helix

30.
The bases present
in DNA are:
Adenine
Guanine
Cytosine
Thymine

31.
Each strand has got a polarity or direction
Each strand has a 3'-end and a 5'-end
S − P − S − P − S − P − S − P
B
B
B
B
B
B
B
B
P − S − P − S − P − S − P − S
5’ End
5’ End
3’ End
3’ End

32.
The two strands are anti-parallel i.e. they
are parallel but run in opposite directions
At 5'-end, –OH group attached to carbon
atom 5 of the sugar is not esterified
At 3'-end the –OH group attached to
carbon atom 3 of the sugar is not esterified

33.
There are two hydrogen bonds between adenine
and thymine (A=T), and three between guanine
and cytosine (G≡C)
All the bases in the molecule take part in
hydrogen bonding with complementary bases on
the opposite strand
The bases are present in the interior of the
molecule while the sugar and phosphate groups
are present on the outer side

34.
5’ 3’
3’ 5’
(b)(a)

35.
The two strands are not straight
They are wound around each other to
form a double helix

36.
The double helix looks
like a twisted ladder

37.
Each turn of the helix contains ten base
pairs
It has a pitch of 3.4 nm
The diameter of the helix is 2 nm
The helix is right-handed

38.
Two grooves are seen in the double helix
These are termed as the major groove and
the minor groove
The grooves are present between the
glycosidic bonds on the opposite strands

39.
3.4 nm
(pitch) 3.4 nm (Pitch)
2 nm
(Diameter)

40.
Richard Dickerson found a slightly different
structure while studying DNA crystals
The structure found by Dickerson was named
as A-DNA, and that described by Watson and
Crick was termed as B-DNA
A third type of structure was found by
Alexander Rich which was named as Z-DNA

41.
B-DNA is the commonest type of DNA
A-DNA is formed when the environment is
less humid
Z-DNA is formed when pyrimidine and
purine bases alternate in a DNA strand

42.
B-DNA A-DNA Z-DNA

43.
A-DNA B-DNA Z-DNA
EMB-RCG
Direction of Right- Right- Left-
helix handed handed handed
Minor groove Wide Narrow Very narrow
Major groove Narrow Wide Flat
Glycosidic bond syn anti syn (purines)
anti (pyrimidines)
Number of base
pairs per turn 11 10 12
Rise per base pair 0.25 nm 0.34 nm 0.37 nm
Rise per turn (pitch) 2.7 nm 3.4 nm 4.4 nm
Diameter 2.3 nm 2.0 nm 1.8 nm
Important features of A-, B- and Z-DNA

44.
Sense and anti-sense
Genetic information is present on one
strand of DNA which is known as the
sense strand
The other strand has a complementary
sequence of bases, and is known as the
anti-sense strand

45.
During replication, the two strands
separate, and each serves as a template
A new strand having a complementary
base sequence is synthesized on each
template strand
Thus, the new DNA becomes an exact
replica of the original DNA

46.
The DNA is combined with a nearly equal
amount of proteins to form nucleoproteins
The predominant proteins are histones which
are of five types – H1, H2A, H2B, H3 and H4
The histones are basic proteins rich in lysine
and arginine

47.
The positively charged amino acids interact with
negatively charged phosphate groups of DNA
The basic amino acids are present mainly in the
N-terminal and C-terminal regions
The inner core of histones contains non-polar
amino acids which form a globular structure

48.
Two molecules each of histones H2A, H2B, H3
and H4 form an octamer around which DNA is
wrapped in two coils to form a
nucleosome
Histone octamer
DNA
Nucleosome

49.
Histone octamer
DNA
H1Chromatosome
A nucleosome associated with histone
H1 is called a chromatosome

50.
― Linker DNA
Polynucleosome
A series of
nucleosomes (“beads
on a string”) form a
polynucleosome
The DNA between two
nucleosomes is known
as linker DNA

51.
Nuclesomes (10 nm wide) condense to form
30 nm wide nucleofilaments
In this way, the linear DNA becomes highly
compact
Even higher compactness is achieved by
looping of nucleofilaments
The loops associate with some scaffold
proteins to form a chromosome

52.
Nucleofilament Chromosome

53.
Many non-histone proteins are also associated
with DNA in small amounts
They have a bearing on various functions like
replication and transcription
Human beings have 23 pairs of chromosomes
Each chromosome consists of a single molecule
of double-helical DNA along with several proteins

54.
Most of the DNA present in a cell is
supercoiled (superhelical)
In supercoiled DNA, the axis of the double
helix is bent and twisted upon itself
In negatively supercoiled DNA, the twists are
right-handed
Most of the naturally occurring DNA is
negatively supercoiled

55.
Circular DNA (relaxed)
Circular DNA
(negatively
supercoiled)
Circular DNA
(positively
supercoiled)

56.
Ribonucleic acid (RNA)
RNA is also a polymer of mononucleotides
The bonds between the mononucleotides
are similar to those in DNA
However, RNA differs from DNA in some
ways

57.
EMB-RCG
Differences between RNA and DNA
DNA RNA
Sugar Deoxyribose Ribose
Pyrimidine
bases
Cytosine
and thymine
Cytosine
and uracil
Number of
strands
Two One
Chargaff’s
rule
Followed Not followed

58.
EMB-RCG
The RNA strand may be folded upon itself
Intra-strand hydrogen bonds may be
formed between complementary bases
present in the same strand
This may give a double-stranded look in
certain regions of the molecule

59.
There are three types of RNA:
Messenger RNA (mRNA)
Transfer RNA (tRNA)
Ribosomal RNA (rRNA)

60.
Structure and functions of different types of RNA
EMB-RCG
Type Structure Function
mRNA
Single,
uncoiled
strand
Transmits information
from DNA and serves as
a template for protein
synthesis
tRNA
Single strand
folded back
on itself
Brings amino acids to
ribosomes for protein
synthesis
rRNA Globular
rRNA and proteins make
up ribosomes

61.
Messenger RNA
Messenger RNA carries message from the
nucleus to the ribosomes
Genetic information is present on the sense
strand of DNA in the form of genes
A gene is a part of the sense strand having
a specific nucleotide sequence

62.
The gene contains coded information for
the synthesis of a particular protein
Each mRNA molecule is a transcript of the
sense strand of a particular gene
Its nucleotide sequence is complementary
to that of the sense strand of the gene

63.
EMB-RCG
At its 5'-end, mRNA possesses a 7-
methylguanosine triphosphate cap
The cap helps the protein-synthesizing
machinery to identify the mRNA
At its 3'-end, it has a poly-A tail made up
of several adenylate residues
The tail stabilizes the structure of mRNA

64.
The mRNA molecule is initially synthesized
in eukaryotes as a precursor
The precursor is heterogeneous nuclear
RNA (hnRNA) or pre-mRNA
hnRNA is much bigger than the final mRNA

65.
hnRNA is processed to form mRNA
The cap and tail are added during
processing
Many nucleotides are removed during
processing

66.
Transfer RNA
tRNA is made up of about 75 nucleotides
Its molecular weight is about 25,000
It transports amino acids from cytosol to
ribosomes for protein synthesis

67.
A given tRNA is specific for one amino acid
Proteins are synthesized from 20 amino
acids
Therefore, there are at least 20 species of
tRNA

68.
Like other RNAs, tRNA is single-stranded
Hydrogen bonds are formed between
complementary bases on the same strand
This gives rise to secondary and tertiary
structures

69.
5’-End
3’-End
Secondary structure is folded upon itself to
form an L-shaped tertiary structure

70.
At the 3'-end, the last three nucleotides
are –C–C–A
The amino acid is attached to the
terminal adenylate residue
The 3'-end is known as the acceptor
arm of tRNA

71.
Pseudouridine (y) loop
The tRNA molecule has three
loops (or arms) known as:
Anticodon loop
Dihydrouracil (DHU) loop

72.
The anticodon loop contains a triplet of
nucleotides known as anticodon
The anticodon is complementary to a
codon on the mRNA
As there is only one anticodon on a tRNA,
it is specific for one amino acid

73.
Ribosomal RNA
rRNA is a structural constituent of
ribosomes
The ribosomes are made up of 40S
subunit and 60S subunit in eukaryotes
Each subunit is made up of some poly-
peptides and some molecules of rRNA

74.
Eukaryotes have four types
of rRNA differing in size:
5S rRNA
5.8S rRNA
18S rRNA
28S rRNA

75.
5.8S, 18S and 28S rRNA are formed
from a single 45S precursor
The 5S rRNA is formed as such

76.
rRNA molecules are extensively
folded

77.
rRNA molecules combine with the poly-
peptides to form globular ribosomal subunits
At the time of protein synthesis, the two
subunits combine to form the ribosome
mRNA and tRNAs bind to the ribosome
to synthesize a protein
EMB-RCG

78.
Ribosome
60S
40S