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NUCLEIC ACIDS

I.

II.

GENERAL DESCRIPTION
Polymeric molecules in which repeating unit is a nucleotide
Discovered by Swiss physiologist, Friedrich Miescher (1844-1895) in 1969 while studying the
nuclei of WBCs
The fact that they were initially found in the cell nuclei and were acidic accounts for the name
nucleic acid
TYPES OF NUCLEIC ACIDS
Phosphate

Base

Sugar

FIGURE 1 Components of a Nucleic Acid (DNA)

Backbone of DNA/RNA always the same

VARIABLE: A, U, C, G, T

FIGURE 1A Components of a Nucleic Acid

1. Deoxyribonucleic acid (DNA)


Nearly all are found within the cell nucleus
Primary function is the storage and transfer of genetic information (is widely used directly to
control many functions in the living cells)
It is passed from existing cells to new cells during cell division
2. Ribonucleic acid (RNA)
Occurs primarily in all parts of the cell
Primarily functions in protein synthesis, the molecules that carry out essential cellular functions

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FIGURE 1B Ribonucleotide (RNA) and Deoxyribonucleotide (DNA)

BASIS
Sugar
Bases
Strands
# of nucleotides

RNA
Ribose
Cytosine and Uracil
Single stranded
Much smaller than DNA molecules

DNA
Deoxyribose
Cytosine and Thymine
Double stranded

TABLE 1 Major differences between RNA and DNA

III.

NUCLEOTIDES: Building Blocks of Nucleic Acids


Molecule composed of a pentose sugar bonded to both a phosphate group and a nitrogencontaining heterocyclic base

FIGURE 2A Building Blocks of Nucleic Acids

(Fused ring)
(Single hetero cyclic ring)
FIGURE 2B General Structure of Nitrogen Bases

A. 3 PARTS OF NUCLEOTIDES:
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FIGURE 3A Parts of Nucleotides

1. Pentose Sugar
Sugar unit of nucleotide is either the pentose ribose (RNA) or 2-deoxyribose (DNA)
2. Nitrogen-containing bases/Heterocyclic base
i.
Purine
o Bi-cyclic base with fused five-and-six member rings
a. Adenine (A): 6-amino-purine
b. Guanine (G): 2-amino-oxypurine
ii.

Pyrimidine
o Monocyclic base with a six-member ring
o RNA: Cytosine and Uracil
o DNA: Cytosine and Thymine
a. Thymine (T): 2,4-dioxy-5-methylpyrimidine
b. Cytosine (C): 2-oxy-4-aminopyrimidine
c. Uracil (U): 2,4-dioxypyrimidine

3. Phosphate
Third component of nucleotide, derived from phosphoric acid (H3PO4)
An important nucleotide is adenosine monophosphate (AMP) formed from a reaction of
adenosine (a nucleotide) and one molecule of phosphoric acid

B. NUCLEOTIDE FORMATION
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FIGURE 4 Nucleotide Formation

Important characteristics of this combining of three molecules into one molecule (nucleotide) are:
1. Dehydration (formation of water molecule) occurs at two locations: between the sugar and base,
and between the sugar and phosphate.
2. The base is always attached at the C1 position of the sugar. For purine bases, attachment is
through N9 for pyrimidine bases, N1 is involved. The C1 carbon atom of the ribose unit is always
in configuration.
3. The phosphate group is usually attached to the sugar at C5 position through the phosphateester-linkage
C. NUCLEOTIDE NOMENCLATURE
1. All of the names end in 5-monophosphate, which signifies the presence of a phosphate group
attached to the 5-carbon/atom of ribose or deoxyribose
2. Preceding the monophosphate ending is the name of the base present in the modified form. The
suffix osine is used for purine bases, the suffix idine with the pyrimidine bases.
3. The prefix deoxy at the start of the name signifies that the sugar present is deoxyribose, when
no prefix is used, the sugar is ribose.
4. The abbreviations in the table for the nucleotides come from the one-letter symbol for the bases
(A, C, G, T and U); the use of MP for monophosphate and a lower case d at the start of the
abbreviation whenever deoxyribose is the sugar
BASE
DNA Nucleotides
Adenine
Guanine
Cytosine
Thymine
RNA Nucleotides
Adenine
Guanine
Cytosine
Uracil

SUGAR

NUCLEOTIDE NAME

ABBREV.

Deoxyribose
Deoxyribose
Deoxyribose
Deoxyribose

Deoxyadenosine 5-monophosphate
Deoxyguanosine 5-monophosphate
Deoxycytidine 5-monophosphate
Deothymidine 5-monophosphate

dAMP
dGMP
dCMP
dTMP

Ribose
Ribose
Ribose
Ribose

Adenosine 5-monophosphate
Guanosine 5-monophosphate
Cytidine 5-monophosphate
Uridine 5-monophosphate

AMP
GMP
CMP
UMP

TABLE 2 Names of Eight Nucleotides found in DNA and RNA

D. PRIMARY STRUCTURE OF NUCLEIC ACIDS


Nucleic Acid Backbone
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o
o

The alternating sugar phosphate chain in nucleic acid structure.


Constant all throughout the entire structure

DNA Backbone
RNA Backbone

Deoxyribo
se

Phospha
te

Deoxyribos
e

Phospha
te

Deoxyribo
se

Ribose

Phospha
te

Ribose

Phospha
te

Ribose

FIGURE 5 Directionality of Nucleic Acid Backbone

PRIMARY STRUCTURE OF A NUCLEIC ACID: The Sequence of Nucleotides in the Molecule


Because the sugar-phosphate backbone of a given nucleic acid does not vary, the primary
structure of the nucleic acid depends only on the sequence of the bases present.
1. Each non-terminal phosphate group of the sugar-phosphate backbone is bonded to two sugar
molecules through a 35-phosphodiester linkage. There is a phosphoester bond to the 5 carbon
of one sugar unit and a phosphoester bond to the 3 carbon of the other sugar.
2. A nucleotide chain has directionality: one end of the nucleotide chain, the 5 end, normally
carries a free phosphate group attached to the 5 carbon atom. The other end of the nucleotide
chain, the 3 end, normally has a free hydroxyl group attached to the 3 carbon atom. By
convention, the sequence of bases of a nucleic acid strand is read from the 5 end to the 3 end.
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3. Each non-terminal phosphate group in the backbone of a nucleic acid carries a -1 charge. The
parent phosphoric acid molecule from which the phosphate was derived originally had three
OH groups. Two of these become involved in the 3,5-phosphodiester linkage. The remaining
OH group is free to exhibit acidic behavior that is, to produce a H+ ion.

FIGURE 5A Nucleotide Sequence

E. THE DNA DOUBLE HELIX


The Watson-Crick Model of DNA
Proposed a double-coiled consisting of two strands intertwined around one another and held
together by hydrogen bonds, much like two entwined rails from spiral staircase
The sugar-phosphate backbones of the two DNA strands from the outside of the helix
The bases (side chains) of each backbone extend inward toward the bases of the other
strand.
The anti-parallel nature of the two polynucleotide chains in DNA double helix means that
there is a 5 end and a 3 end at both ends of the double helix
If the chain is untwisted and straightened out, it can be represented as Figure 4A.
The solid lines ordinary bonding
Dotted lines hydrogen bonding
o A and T 2 double bonds
o G and C 3 double bonds
All DNA molecules have the same sequence of deoxyribose and phosphates in the ladder part
of the chain, the difference lies in the order of the adenine, thymine, cytosine and guanine
parts of the chain makes up genetic code.
o DNA molecule (Human) 5 billion nucleotides
o DNA molecule (bacteria/virus) 5,500 nucleotides

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FIGURE 4A Watson-Crick Model of the DNA

FIGURE 5B Hydrogen Bonded Base Pairs

BASE PAIRING
Chargaffs Rule
o Number of Purine molecules = Number of Pyrimidine molecules
A
=
T
G

C
Complementary Bases
o Specific pairs of bases in nucleic acid structures that hydrogen-bond to each other
o Two strands of DNA in double helix are not identical they are complementary (that
means if you know the order of bases in one strand, you can predict the order of
bases in the other strand).
o A mnemonic device for recalling base pairing combinations in DNA and RNA
involves listing the base in alphabetical order. Then the first and last bases pair, and
so the middle.
o DNA A
C
G
T
o RNA A
C
G
U
o In specifying base sequence of segment of strand of DNA or RNA, the bases are listed
in sequential order (using their one-letter abbreviations) in the direction from 5 end
to 3 end of the segment

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F. REPLICATION OF DNA MOLECULES:

CHROMOSOMES
Individual DNA molecule bound to a group of molecule
These are nucleoproteins; they are combinations of nucleic acid (DNA) and various proteins.
15% by mass DNA and 85% by mass proteins

FIGURE 6A Chromosomes

DNA REPLICATION
Process by which DNA molecules produce exact duplicates of themselves.
Prior to division, cell has to duplicate its DNA
Semi-conservative replication
o Produces two new DNAs (daughter strand DNAs) identical to each other and exact copies
of the original parent DNA
o Strands are identical to original due to complementary base pairing
Complementary base pairing ensures the correct placement of bases in the new DNA strands
Helicase
o Unwinds/uncoils DNA helix and splits double strand
Single-Strand Binding Proteins (SSB)
o A single-strand binding-protein stabilizes the separated strands, and prevents them from
recombining, so that the polymerization chemistry can function on the individual strands.
DNA polymerase
o Catalyzes formation of phosphodiester bonds between the nucleotides
o Energy is provided to join each new nucleotide to the backbone of a growing DNA strand
o Catalyzes the replication process at each of these open DNA sections (replication forks)
o Catalyzes only phosphodiester bonds between the 5-phosphate of one of the nucleotide
and the 3-hydroxyl of the next, which means that DNA polymerases have to move in
opposite directions along the separated strands of DNA
Adds nucleotides in 5 3 direction (leading strand) movement towards
helicase (replication fork)
o Binds complementary bases
a. Leading strand
Replication is continuous
b. Lagging strand
Synthesized in the opposite direction
Formed in short segment of 100-200 nucleotides
Grows in direction of 53 because DNA polymerase III only works in the 53
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RNA Primase
o Places an RNA primer near fork
o Bonds the RNA nucleotides together
RNA primer
o Short sequence of RNA nucleotides, complementary to a small, initial section of the DNA
strand being prepared for replication
o Adds short RNA strand to DNA
Allows DNA polymerase to start on lagging strand
o Made by adding complimentary RNA nucleotides to the lagging DNA strand by hydrogen
bonding of the bases
RNA has U instead of T
o Enzymatically removed and replaced with an appropriate sequence of DNA nucleotides

FIGURE 7A Initiation of Replication by RNA primer


and RNA primase

DNA polymerase III


o Initiates replication process
o Adds nucleotides to the lagging strand until it reaches the next primer
o Bonds DNA nucleotides to the RNA primer
o Adds nucleotides in 5 3 direction (lagging strand) movement away helicase
(replication fork)
o These enzymes also check for errors (roughly ten per billion), and make corrections.

FIGURE 7B Formation of Okazaki fragments

DNA polymerase I
o Removes the RNA primers creating Okazaki fragments and replaces it with DNA
Okazaki fragments = short lengths of DNA formed between RNA primers
DNA ligase
o Adds DNA nucleotides to fill the gaps between Okazaki fragments and connect lagging
strand fragments by creating sugar-phosphate bond

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FIGURE 7C Replication fork, Leading and Lagging strand

FIGURE 7D Summary of DNA Replication

RIBONUCLEIC ACIDS (RNA)


a. rRNA
o Combines with a series of proteins to form complex structures called ribosomes, that
serves as the physical sites or platform for protein synthesis
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Most abundant in cells (75% by mass)

b. mRNA
o Carries genetic information (instructions for protein synthesis) from DNA to ribosome
o Messenger and its precursor 5-10%
o Primary Transcript RNA (ptRNA)
Material from which messenger RNA is made
c. tRNA
o Delivers specific individual amino acids to the ribosomes, the sites of protein synthesis
o Constitutes 10-15% cellular RNA
c. OVERVIEW OF PROTEIN SYNTHESIS 2 STEPS

FIGURE 8A Protein Synthesis

1. TRANSCRIPTION: RNA Synthesis


Process by which DNA directs the synthesis of RNA molecules that carry the coded information
needed for protein synthesis
The mechanics of transcription are in many ways similar to those of DNA replication
Begins when the section of a DNA molecule that contains the gene to be copied unwinds, which
contains a transcription bubble
Steps:
a. A portion of the DNA double helix unwinds, exposing some bases. The unwinding process is
governed by the enzyme RNA polymerase rather than by DNA helicase.
b. Free ribonucleotides align along one of the exposed strands of DNA bases forming new base
pairs. In this process, U rather than T aligns with A in the base-pairing process. Because
ribonucleotides rather than deoxyribonucleotides are involved in the base-pairing, ribose
rather than deoxyribose, becomes incorporated into the new nucleic acid backbone.
c. RNA polymerase links the aligned ribonucleic acids.
d. Transcription ends when the RNA polymerase encounters a sequence of bases that is read
as a stop signal. The newly formed RNA molecules and the RNA polymerase enzyme are
released, and the RNA polymerase enzyme are released and the DNA then rewinds to reform
the original double bonds.
In DNA-RNA base pairing, the complementary base pairs are:
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DNA
A
G
C
T

RNA
U
C
G
A

RNA molecules contain the base U instead of T


o The primary function of mRNA molecules is to direct the synthesis of the many different
proteins needed for cellular function. Within a DNA strand are instructions for the
synthesis of numerous mRNA molecules. During transcription, the DNA molecule
unwinding is controlled by RNA polymerase and occurs only at the particular spot where
the appropriate base sequence is found for the mRNA (and protein) of concern. Such
short segments of DNA, containing instructions for the formation of particular mRNAs
are called genes
o Gene is a segment of DNA molecule that contains the base sequence for the production
of single specific protein molecule.
It is now known that not all bases in a gene convey genetic information. Instead, a gene is
segmented in portions called exons that contain genetic information and portions called
introns that convey genetic information
EXON DNA segment that conveys genetic information and helps express a genetic message.
INTRON DNA segment that does not convey genetic information and interrupt a genetic
message.
Both exons and introns of a gene are transcribed during production of primary transcript RNA
(ptRNA) or pre-mRNA. The ptRNA is then edited, under the direction of enzymes to remove
introns. The remaining exons are joined together to form a shortened RNA strand that carries
the genetic information of the transcribed gene. This edited RNA is the messenger RNA
(mRNA) that serves as a blueprint for protein assembly.
2. TRANSLATION
Process by which the codes within the RNA molecules are decipheral and a particular molecule
is formed.
Process whereby the nucleotide sequence in an mRNA molecule specifies the amino acid
sequence of protein. Ribosome in the cytoplasm carries out translation.
CODON
o Sequence of three nucleotides in an mRNA molecule that codes for a specific amino acid
ANTICODON
o Nucleotide sequence in tRNA that is complementary to the mRNA for the amino acid
which bonds to the tRNA
5 general Steps in Translation
a. ACTIVATION OF tRNA
o An amino acid interacts with an activator molecule (ATP) to form a highly energetic
complex. This complex that reacts with an appropriate tRNA molecule to produce an
activated tRNA molecule that has an amino acid covalently bonded to it at its 3 end
through an ester linkage
b. INITIATION
o Begins with mRNA which attaches itself to the surface of a small ribosomal subunit such
that its first codon, which is always the initiating codon AUG; occupies a site called the P
site.
c. ELONGATION
o The polypeptide continues to grow by way of translation until all necessary amino acids
are in place and bonded to each other.
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d. TERMINATION
o Appearance in the mRNA codon sequence of one of the three stop codons terminates the
process
e. POST-TRANSLATION PROCESSING
o Some modification of proteins usually occurs after translation
THE GENETIC CODE
1. The genetic code is highly degenerated that is many amino acids designated by more than
one codon. Codons that specify the same amino acids are called synonyms
2. There is a pattern to the arrangement of the genetic code table
3. 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
4. An initiation codon exists
o The existence of stop codons suggests the existence of start codons
o The one initiation codon is AUG
First Position (5
end)
A

A
Lys
Asn
Lys
Asn
Gln
His
Gln
His
Glu
Asp
Glu
Asp
Stop
Typ
Stop
tyr

Second Position
C
G
U
Thr
Arg
Ile
Thr
Ser
Ile
Thr
Arg Met/Start
Thr
Ser
Ile
Pro
Arg
Leu
Pro
Arg
Leu
Pro
Arg
Leu
Pro
Arg
Leu
Ala
Gly
Val
Ala
Gly
Val
Ala
Gly
Val
Ala
Gly
Val
Ser
Stop
Leu
Ser
Cys
Phe
Ser
Trp
Leu
Ser
Cys
Phe

Third Position (3
end)
A
C
G
U
A
C
G
U
A
C
G
U
A
C
G
U

TABLE 3 mRNA codons: The Genetic Code for Amino Acids

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FIGURE 8C Steps in Transcription

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FIGURE 8D (i) Steps in Transcription

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FIGURE 8D (ii) Steps in Transcription

GENETIC MUTATIONS:
Occurs if one of the code letters is omitted or if one is added or if the order of the code letters is
rearranged. Such a change in the sequence of nucleotides may:
1. Give no detectable effect, particularly of the change is in the third letter of the code.
2. Cause a different amino acid to be incorporated into the chain (the results may be
acceptable, or totally unacceptable to the function of the protein)
3. Cause the termination of the chain prematurely so that the protein cannot normal.
Causes:
1. Exposure to radiation
2. Because of naturally occurring radiation and cosmic rays
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3. Exposure to certain chemicals


Types:
1. Frameshift
Usually severe, producing a completely nonfunctional protein.
If the letters are read three at a time and one is deleted, the second sentence
becomes meaningless.
Original DNA: THE BIG RED ANT ATE ONE FAT BUG
Frameshift mutation: THB IGR EDA NTA TEO NEF ATB UG?
2. Point Mutation
Involves a single nucleotide, thus a single amino acid.
In the sentence below, eliminating one letter does not change in the remaining
three-letter words and therefore may not cause a significant change in the
meaning of the sentence.
Original DNA: THE BIG RED ANT ATE ONE FAT BUG
Point mutation: THA BIG RED ANT ATE ONE FAT BUG
3. Silent, Missense, and Nonsense Mutations
a. Missense mutation
b. Nonsense mutation
c. Silent mutation
GENETIC DISEASES:
Mostly caused by defective gene resulting in a loss of activity of some enzyme
1. CYSTIC FIBROSIS
Thick mucus develops and results in bronchia. Obstruction early in childhood infection occurs
and becomes difficult to eradicate even with antibiotics. When such an infection develops in the
lungs, the subsequent inflammatory reaction results in the destruction of bacteria. Leukocytes
and tissue, the process of cellular destruction releases DNA, which in turn substantially
increases the viscosity of the mucus.
One of the most commonly inherited diseases in children. Thick mucus secretions make
breathing difficult and block pancreatic function.
Treatment DNAse, an enzyme that degrades extracellular DNA nut has no effect on the DNA
within intact cells
2. PHENYLKETANURIA (PKU)
Results when the enzyme phenylalanine hydroxylase is absent. A person with PKU cannot
convert phenylalanine to tyrosine, and so the phenylalanine accumulates in the body, resulting
in injury to the nervous system. In children up to 6, an accumulation of phenylalanine leads to
retarded mental development. It can be readily diagnosed from a sample of blood or urine.
Treatment Consists of giving the affected person a diet low in phenylalanine and adding
tyrosine to the diet.
3. SICKLE CELL ANEMIA
Sickle cells (containing hemoglobin) are fragile than normal red blood cells which leads to
anemia. They can also occlude capillaries, leading to thrombosis. Sickle cells in the capillaries
cause slowing and sludging of the red blood cells in the capillaries, with resulting hypoxia of the
tissues which in turn produces symptoms like fever, swelling, and pain in various parts of the
body.
A defective Hgb from a mutation in a gene in chromosome 11 decreases the oxygen carrying
ability of RBC which takes on a sickle shape, causing anemia and plugged capillaries from RBC
segregation.

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4. GALACTOSEMIA
Results from the lack of enzyme uridyl transferase, which catalyzes the formation of glucose
from galactose. This disease may result in an increased concentration of galactose in the blood.
Galactose in the blood is reduced in the eye to galacticol, which accumulates and causes a
cataract, even liver failure and mental retardation will occur.
Transfer of enzyme requuired for the metabolism of glucose-1-phosphate is absent.
Accumulation of Gal-1-P leads to cataracts and mental retardation.
Treatment Administration of galactose free diet
5. WILSONS DISEASE
Caused by the bodys failure to eliminate excess Cu 2+ ions because of a lack of ceruplasmin or
failure in the bonding of copper ions to the copper-bonding globulin or both. In this disease,
copper accumulates in the liver, kidneys and brain. Increased copper in the kidneys may lead to
damage of the renal tubules, leading to increased urinary output of amino acids and peptides.
6. ALBINISM
Caused by lack of enzyme tyrosinase, which is necessary for the formation of melanin, the
pigment of the hair, skin, and eyes. Although the disease is not serious, persons affected by it are
very sensitive to sunburn.
7. HAEMOPHILIA
Caused by a missing protein, an antihemophilic globulin, which is important in the normal
clotting process of the blood. Consequently, any cut may be life threatening to hemophiliacs, but
the primary damage is the crippling effect of repeated episodes of internal bleeding into body
joints.
One or more defective blood clotting factors lead to poor coagulation, excessive bleeding, and
internal hemmorhages.
8. MUSCULAR DYSTROPHY (MD)
Duchennes muscular dystrophy, one of 10 forms of MD, is caused by the lack of protein called
dystrophin, as caused by a mutation in the X chromosome. This disease primarily affects boys at
about age 5 with death by age 20. It causes progressive weakness and muscle wasting.
9. DOWN SYNDROME
The leading cause of mental retardation, occuring in about 1 in every 100 live births, although
the mothers age strongly influences its occurrence. Mental and physical problems including
heart and eye defects are the result of the formation of three chromosomes, usually
Chromosome 21, instead of a pair.
10. FAMILIAL HYPOCHOLESTEREMIA
A mutation of a gene on chromosome 19 results in high cholesterol levels that leads to early
Coronary Heart Disease in people 30-40 years old.
11. HUNTINGTONS DISEASE (HD)
Appearing in middle age, affects the nervous system, leading to total physical impairment. It is
the result of a mutation in a gene on chromosome 4, which can now be mapped to test people in
families with HD.
12. TAY-SACHS DISEASE
Hexosamindase A is defective, causing an accumulation of gangliosides resulting in mental
retardation, loss of motor control, and early death.
TREATMENT OF GENETIC DISEASES:
1. Correct the metabolic consequences of the disease by supplying the missing product.
2. Replace the missing enzyme or hormone.
3. Remove excessive stored substances
4. Correct the major genetic abnormality.

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