NUCLEIC ACIDS

1- Definition
2- Classification and biological functions
2.1 DNA
2.2 RNA
3- Components of Nucleic acids: Structures and Nomenclatures
3.1 N-bases
3.1.1 Purine bases: adenine, guanine
3.1.2 Pyrimidine bases; cytosine, uracil, thymine
3.2 Pentose sugars: ribose, 2-deoxyribose
3.3 DNA & RNA nucleosides
4- Basic Differences between DNA and RNA
4.1 Pentose Sugar
4.2 N-bases
4.3 Number of Strands per Molecule
4.4 Secondary Structure
4.5 Location in the Cell
4.6 Biological Functions
5- The Structural Organization of the DNA
5.1 Primary Structure
5.2 Secondary Structure
5.3 Tertiary Structure
5.4 Quaternary Structure
6- Types of RNA, Structural Features and Functions
6.1 Messenger RNA (mRNA)
6.2 Ribosomal RNA (rRNA)
6.3 Transfer RNA (tRNA)
7- Central Dogma of Molecular Genetics
7.1 DNA replication
7.2 Transcription
7.3 Translation
8- Gene Mutations and Mutagens
8.1 Mutations due to Physical Agents
8.2 Mutations due to Chemical Agents
8.3 Mutations due to Viral Agents
9- DNA Repair Mechanisms
9.1 Enzymes
9.2 Free Radical Scavengers/Antioxidants
9.3 Dark repair Mechanism
 The Molecules of Heredity
➢ Each cell of our bodies contains thousands of different proteins.
➢ How do cells know which proteins to synthesize out of the extremely large
number of possible amino acid sequences?
➢ From the end of the 19th century, biologists suspected that the
transmission of hereditary information took place in the nucleus, more
specifically in structures called chromosomes.
➢ The hereditary information was thought to reside in genes within the
chromosomes.
➢ Chemical analysis of nuclei showed chromosomes are made up largely of
proteins called histones and nucleic acids.
➢ By the 1940s, it became clear that deoxyribonucleic acids (DNA) carry the
hereditary information.
➢ Other work in the 1940s demonstrated that each gene controls the
manufacture of one protein.
➢ Thus the expression of a gene in terms of an enzyme protein led to the
study of protein synthesis and its control.
NUCLEIC ACIDS
- are molecules that store the patterns of life and these patterns are
passed from one generation to the next. They act as repositories
and transmitters of genetic information
- a polymer in which the monomer units are nucleotides
- nucleotides joined together by phosphodiester bonds
- found in cells as nucleoproteins
- they are also called polynucleotides
 Two Types of Nucleic Acids:

1. DNA: Deoxyribonucleic Acid:

- Found within cell nucleus, storage and transfer of genetic information
(genotype)
- Passed from one cell to other during cell division
- sugar composed of α-deoxyribose

2. RNA: Ribonucleic Acid: Occurs in all parts of cell

Primary function is to synthesize the proteins, transmits the information
to make proteins, the molecule responsible for the visible or observable
traits (phenotype)
- sugar composed of β-ribose
Pentose sugar:
RNA – ribose DNA – deoxyribose
Structural difference:
—OH group present on carbon 2’ in ribose
—H atom in 2-deoxyribose

Phosphate- third component of a nucleotide, is derived from phosphoric acid.

Under cellular pH conditions, the phosphoric acid is fully dissociated to
give a hydrogen phosphate ion (HPO42-)
Nitrogen-Containing Heterocyclic Bases

1. Purine Bases
adenine (A) and guanine (G)
2. Pyrimidine Bases
thymine (T), cytosine (C), and uracil (U)
Adenine (A), guanine (G), and cytosine (C) are found in both DNA and RNA.

Uracil (U): found ONLY in RNA

Thymine (T) found ONLY in DNA.
NUCLEOSIDE – a nucleic acid constituent consisting of a sugar residue bonded
to a heterocyclic purine or pyrimidine base.
NUCLEOTIDE – a nucleic acid constituent consisting of a sugar residue bonded
to both a heterocyclic purine or pyrimidine base and to a phosphate
group
nucleoside = N-Base + Sugar
nucleotide = N-Base + Sugar + Phosphate
nucleic acid = A chain of nucleotides

Difference Between Nucleotides and Nucleosides | ProtonsTalk

 Nucleic acids (xaktly.com)

Nucleoside
formation

Nucleotide
formation

dna - Misunderstanding about nucleotide biosynthesis - Biology Stack Exchange

Building blocks of DNA and RNA
 Differences between DNA and RNA
DNA RNA
Pentose Sugar deoxyribose Ribose
N-Bases A,G,C,T A,G,C,U
Number of Strands per structured as a double helix (two strands Single stranded
Molecule of DNA winding around each other)
Secondary Structure two DNA strands, running in opposite RNA bases form hydrogen
directions, that are held together by bonds with complementary
complementary base pairing and twisted bases on the same strand
into a double helix forming hairpin loops

Location in the Cell Mostly found in nucleus and some in Formed in the nucleolus of cells
mitochondria and moves into cytoplasm
depending on type of RNA
Biological Functions Replicates and stores genetic Carry out instructions encoded
information in DNA
 STRUCTURAL ORGANIZATION OF THE DNA

➢ Primary
➢ Secondary
➢ Tertiary
➢ Quaternary

❑ Primary structure is the linear sequence of nucleotides, secondary structure

involves small local folding motifs, and tertiary structure is the 3D folded
shape of nucleic acid molecule. In general, quaternary structure refers to
3D interactions between multiple subunits.
Primary Structure for DNA: - Describes the sequence and relative contents
or % composition of the DNA molecule
2 important features of all polynucleotides
a. A polynucleotide has a sense of
directionality
b. A polynucleotide has individuality,
determined by the sequence
of its bases (the nucleotide sequence)
For nucleic acids, primary structure is the
sequence of nucleotides, beginning with
the nucleotide that has the free 5’ terminus.
➢ The strand is read from the 5’ end to the 3’ end.
➢ Thus, the sequence AGT means that adenine (A) is the base at the 5’
terminus and thymine (T) is the base at the 3’ terminus.
➢ 5’ end has free phosphate and 3’ end has a free OH group
Schematic diagram of a nucleic acid
molecule. The four bases of each
nucleic acid are arranged in various
specific sequences.

base sequence is read from the 5’

end to the 3’ end
Comparison of the General Primary Structures of Nucleic Acids and Proteins

The key difference between amino acid and nucleic acid is that amino acid is
the building block of proteins whereas nucleic acids is a macromolecule made
out of nucleotides. Therefore, amino acids are small molecules while nucleic
acids are macromolecules.
Secondary Structure of DNA:
- The ordered arrangement of nucleic acid strands. The double helix model of
DNA 2° structure was proposed by James Watson and Francis Crick in 1953.
Double helix: A type of 2° structure of DNA in which two polynucleotide
strands are coiled around each other in a screw-like fashion.
The secondary structure involves two polynucleotide chains coiled around each
other in a helical fashion
The poly nucleotides run anti-parallel (opposite directions) to each other,
i.e., 5’ - 3’ and 3’ - 5’
The bases are located at the center and hydrogen bonded (A=T and GΞC)
Base composition: %A = %T and %C = %G)
Structure of DNA- double helix (Watson and Crick Model)

The model of DNA established by Watson and Crick

was based on key contributions of other researchers,
including the analysis of the base composition of
DNA. The analysis of DNA from many different
forms of life revealed an interesting pattern. The
relative amounts of each base often varied from one
organism to another, but in all DNA the percentages
of adenine and thymine were always equal to each
other as were the percentages of guanine and
cytosine. For example, human DNA contains 20%
guanine, 20% cytosine, 30% adenine, and 30%
thymine. Watson and Crick concluded from these and
other types of data that DNA is composed of two
strands entwined around each other in a double helix.
Complimentary Base Pairing
A and T pair by forming two hydrogen bonds. G and C pair by forming three
hydrogen bonds.

1733-1529595446316.png (1667×1667) (d1j63owfs0b5j3.cloudfront.net)

DNA Sequence: the sequence of bases on one polynucleotide is complementary
to the other polynucleotide

Complementary DNA strands are strands of DNA in a double helix with base
pairing such that each base is located opposite its complementary base.

Example :
List of bases in sequential order in the direction from the 5’ end to 3’ end of
the segment:
5’-A-A-G-C-T-A-G-C-T-T-A-C-T-3’
Complementary strand of this sequence will be:

3’-T-T-C-G-A-T-C-G-A-A-T-G-A-5’
TERTIARY LEVEL of DNA structure

- Higher-Order Structures of DNA

- The 3-D structure that involves a higher-order folding of elements of
regular secondary structure
- The supercoiling of the DNA
- HISTONES – small proteins that participate in forming the nucleosomal
structure of the chromatin
 Superstructure of Chromosomes

DNA is coiled around proteins called histones.

Histones are rich in the basic amino acids Lys and Arg, whose side chains have
a positive charge.
The negatively-charged DNA molecules and positively-charged histones attract
one another by ionic forces and form units called nucleosomes.
Nucleosome: A core of eight histone molecules around which the DNA helix is
wrapped.
Nucleosomes are further condensed into chromatin.
Chromatin fibers are organized into loops, and the loops into the bands that
provide the superstructure of chromosomes.
QUATERNARY LEVEL of DNA structure

❑ Involves the interaction of the DNA with other macromolecules, specifically

proteins.

❑ This organizational structure allows long stretches of DNA to be tightly

packed in a space of about 2 µm in diameter

❑ Refers to the binding of DNA to histones to form nucleosomes (the basic

repeating subunit of chromatin packaged inside the cell's nucleus), and
then their organization into higher-order chromatin fibers. The
quaternary structure of DNA strongly affects how accessible the DNA
sequence is to the transcription machinery for gene expression.
 Types of RNA Molecules
1. Heterogeneous nuclear RNA (hnRNA)
- Formed directly by DNA transcription.
- Post-transcription processing converts the hnRNA to mRNA
2. Messenger RNA (mRNA)
- Carries instructions for protein synthesis (genetic information)
from DNA
3. Small nuclear RNA (snRNA)
- facilitates the conversion of hnRNA to mRNA.
4. Ribosomal RNA (rRNA)
- Combines with specific proteins to form ribosomes - the physical
site for protein synthesis
5. Transfer RNA (tRNA)
- delivers amino acids to the sites for protein synthesis
mRNA codon

➢ The product of DNA transcription

3'

➢ Carries instructions for protein synthesis from DNA

5'

➢ It contains a sequence of three bases specifying for an amino acid. This

sequence is called a codon.
➢ The mRNA is single-stranded and has a random conformation
➢ The base sequence in mRNA determines the amino acid sequence for the
protein synthesized.
➢ The base sequence of an mRNA molecule involves only 4 different bases - A, C,
G, and U
Codon: A three-nucleotide sequence in an mRNA molecule that codes for a specific
amino acid. Based on all possible combination of bases A, G, C, U” there are
64 possible codes
Genetic code: The assignment of the 64 mRNA codons to specific amino acids 3 of
the 64 codons are termination codons (“stop” signals)
Gene: A segment of a DNA base sequence responsible for the production of a
specific hnRNA/mRNA molecule
tRNA
The only RNA with a specific shape
2 – D structure: cloverleaf 3 – D structure: L-shaped
➢ During protein synthesis, amino acids do not directly interact with the
codons of an mRNA molecule
➢ tRNA molecules act as intermediaries to deliver amino acids to mRNA
➢ The adaptor molecule that recognizes the codon in mRNA and transfers the
amino acid corresponding to the codon
➢ Two important features of the tRNA structure
a. The 3′ end of tRNA is where an amino acid is covalently bonded to it
b. The loop opposite to the open end of tRNA, called the anticodon,
comprises seven unpaired bases
➢ Three unpaired bases constitute the anticodon (a three-nucleotide sequence
on a tRNA molecule that is complementary to a codon on an mRNA
molecule)
➢ Each tRNA is specific for only one amino acid.
➢ Each cell carries at least 20 specific enzymes, each specific for one amino
acid.
➢ Each enzyme recognizes only one tRNA.
➢ The enzyme bonds the activated amino acid to the 3’ terminal -OH group of
the appropriate tRNA by an ester bond.
➢ At the opposite end of the tRNA molecule is a codon recognition site.
➢ The codon recognition site is a sequence of three bases called an anticodon.
➢ This triplet of bases aligns itself in a complementary fashion to the codon
triplet on mRNA.
➢ Contains the anticodon loop ~ a sequence of three bases complementary to
the codon
Ribosomal RNA
➢ RNA that constitutes about 65% of the material in ribosomes, the sites of
protein synthesis.
➢ constitutes 80–85% of the total RNA of the cell
➢ rRNA complexes with proteins to form structures called ribosomes, the site
of protein biosynthesis
➢ rRNA catalyses peptide bond formation.
As amino acids are added along the
growing peptide chain, the rRNA
in ribosome helps peptide bonds
form by catalysing the reaction.

Structure of RNA (A-level Biology) - Study Mind

 THE CENTRAL DOGMA OF GENETICS

Summarizes the mechanisms for transfer of genetic information. The genetic

information flows only in one direction, from DNA, to RNA, to protein, or RNA
directly to protein.
 REPLICATION
➢ Process by which DNA molecules produce exact duplicates of themselves.
➢ The newly synthesized DNA has one new DNA strand and an old DNA strand
During replication process, the strands separate. Each can then act as a
template for the synthesis of a new complimentary strand
Replication fork – point at which DNA double helix is unwinding
DNA Replication is Semiconservative - the two strands of the double helix
separate during DNA replication, and each strand serves as a template from
which the new complementary strand is copied. After replication in this model,
each double-stranded DNA includes one parental or “old” strand and one
daughter or “new” strand. Chapter 9: DNA Replication - Chemistry (wou.edu)
General Overview of a DNA Replication Fork
At the origin of replication, topoisomerase II relaxes the supercoiled chromosome.
Two replication forks are formed by the opening of the double-stranded DNA at the
origin, and helicase separates the DNA strands, which are coated by single-stranded
binding proteins to keep the strands separated. DNA replication occurs in both
directions. An RNA primer complementary to the parental strand is synthesized by
RNA primase and is elongated by DNA polymerase III through the addition of
nucleotides to the 3′-OH end. On the leading strand, DNA is synthesized continuously,
whereas on the lagging strand, DNA is synthesized in short stretches called Okazaki
fragments. RNA primers within the lagging strand are removed by the exonuclease
activity of DNA polymerase I, and the Okazaki fragments are joined by DNA ligase.
Chapter 9: DNA Replication - Chemistry (wou.edu)

Nicks- The gaps or breaks between segments in this daughter strand

Okazaki fragments- the short lengths of DNA that are produced by the
discontinuous replication of the lagging strand.
Leading strand- continuously synthesized strand
Lagging strand- strand requires a slight delay before undergoing replication, and it
must undergo replication discontinuously in small fragments.
 Protein synthesis can be divided into two phases.
1. Transcription – A process by which DNA directs the synthesis of mRNA
molecules
2. Translation – a process in which mRNA is deciphered to synthesize a protein
molecule
 TRANSCRIPTION
the process by which the genetic information contained within DNA is
re-written into messenger RNA (mRNA) by RNA polymerase. This mRNA then
exits the nucleus, where it acts as the basis for the translation of DNA.

FEATURES:
1. There is a start regulated by the promoter region and a stop regulated by
the termination sequences.
2. Transcription copies only one strand of the DNA, the 3’ → 5’ strand.
3. The direction of synthesis is 5’ → 3’. Synthesis is facilitated by the RNA
polymerase.
4. The final product of transcription is the mRNA.
5. mRNA goes to the ribosome for protein synthesis.
5.7 Protein Synthesis – Human Biology (tru.ca)
 TRANSLATION
➢ a process in which mRNA codons are deciphered to synthesize a protein molecule
➢ the process that takes the information passed from DNA as mRNA and turns it
into a series of amino acids bound together with peptide bonds. It is essentially a
translation from one code (nucleotide sequence) to another code (amino acid
sequence).

➢ STEPS of translation process:

a. Activation of tRNA: addition of specific amino acids to the 3’-OH group of
tRNA.
b. Initiation of protein synthesis: Begins with binding of mRNA to small
ribosomal subunit such that its first codon (initiating codon AUG)
occupies a site called the P site (peptidyl site)
c. Elongation: Adjacent to the P site in an mRNA–ribosome complex is A site
(aminoacyl site) and the next tRNA with the appropriate anticodon binds
to it.
d. Termination: The polypeptide continues to grow via translocation until all
necessary amino acids are in place and bonded to each other.
e. Post-translational processing – gives the protein the final form it needs to be
fully functional
5.7 Protein Synthesis – Human Biology (tru.ca)
5.7 Protein Synthesis – Human Biology (tru.ca)
Functions of the RIBOSOMES:
1. Selects appropriate regions on mRNA to begin translation.
2. Maintains proper alignment of codon and anti-codon.
3. Catalyze the formation of peptide bonds.
4. Responsible for a continuous synthetic process.
Synthesis-protein.jpg (1600×1600) (britannica.com)
FIGURE 25.9 The fundamental
process of information
transfer in cells. (1)
Information encoded in the
nucleotide sequence of DNA is
transcribed through synthesis
of an RNA molecule whose
sequence is dictated by the
DNA sequence. (2) As the
sequence of this RNA is read
(as groups of three
consecutive nucleotides) by
the protein synthesis
machinery, it is translated into
the sequence of amino acids in
a protein. This information
transfer system is
encapsulated in what is known
as the central dogma of
molecular biology:
DNA → RNA → protein.
 THE GENETIC CODE

The genetic code is a set of three-letter combinations of nucleotides called

codons, each of which corresponds to a specific amino acid or stop signal.
Characteristics of Genetic Code
The genetic code is almost universal:
The same codon specifies the same amino acid whether the cell is a bacterial
cell, a corn plant cell, or a human cell.

The codon - coding for the amino acid methionine (AUG) functions as
initiation codon.
“Stop” codons (UAG, UAA, and UGA)
- terminate protein synthesis
The vertebrate mitochondrial DNA (mtDNA) genetic code
 Mutation of DNA

➢ An error in base sequence reproduced during DNA replication

➢ Errors in genetic information is passed on during transcription.
➢ The altered information can cause changes in amino acid sequence during
protein synthesis and thereby alter protein function
➢ Involves a change in shape, structure or nucleotide sequence of the DNA
➢ Such changes have a profound effect on an organism.

➢ Two types of mutation origin

a. spontaneous
b. induced by physical and chemical Mutagens
Spontaneous mutations are mutations that occur in the absence of exogenous
agents. They may be due to errors made by DNA polymerases during
replication or repair, errors made during recombination, the movement of
genetic elements, or spontaneously occurring DNA damage.
Methods for Determining Spontaneous Mutation Rates - PMC (nih.gov)

Mutagens
Mutations that are caused by mutagens. A mutagen is a substance or agent
that causes a change in the structure of a gene:
MUTATIONS may be due to
1. Physical Agents
ultraviolet and ionizing radiation -the base most affected by UV
radiation is thymine
2. Chemical agents
-alkylating agents (N-nitrosamines)
-found in cigarette smoke, metabolized by liver enzymes
-deaminating agents (Sodium nitrite) used as a preservative, color
enhancer, and fixative in bacon, smoked fish, tocino, etc.
-intercalating agents (heterocyclic ring molecules which distorts DNA
double helix) includes benzopyrene in automobile exhaust,
benzene – an organic solvent and aflatoxin – a metabolic product
of molds in peanuts, oil and grains
3. Viral agents (oncogenes)- are cancer-causing genes. An oncogene is a
mutated gene that has the potential to cause cancer
POINT MUTATIONS

➢ A point mutation occurs in a genome when a single base pair is added,

deleted or changed
➢ Can be a change in a single base, or addition or removal of one or more
nucleotides in the DNA
➢ May have no effect on the amino acid sequence of the protein. This is most
likely if the substituted base is in the third codon.
➢ Single base changes are of two types
a. transitions – involves a change of a purine to another purine OR a
pyrimidine to another pyrimidine
b. transversions – involves a change of a purine to a pyrimidine and vice
versa
 Repair Mechanisms

1. Enzymes- DNA Polymerases Lambda (λ) and Mu (μ) are members of the X-
Family, and are primarily involved in DNA repair. They detect and repair
distortions caused by mismatched bases inserted during DNA
synthesis.

2. Free-radical scavengers/antioxidants- prevent the formation of free

radicals, and seek and neutralize or repair the damage caused by them

3. Dark repair mechanism- also called Excision repair, a light-independent

repair mechanism that involves three steps: a. recognition of, binding to,
and removal of damaged DNA. b. repair synthesis of excised region by
DNA polymerase and c. ligation by DNA ligase to seal the break.