NUCLEIC ACIDS:

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NUCLEIC ACIDS STRUCTURE and FUNCTION
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• Objectives
• To describe the structure of DNA and RNA
• To explain how the structure of DNA relates to
  the functioning of the gene

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NUCLEIC ACIDS STRUCTURE and FUNCTION
Objectives At the end of these lectures you
should be able to describe - The types of
nucleic acids - The structure of nucleic acids -
The base composition of DNA - The conformations
of DNA - The functions of nucleic acids
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Why study nucleic acids? DNA is the focus of
attention because of its role in carrying and
expressing genetic information. The Human Genome
Project where over 90 (99.9 accuracy) of the
3.2 billion nucleotides have been cloned and
sequenced. The information is hoped, will
revolutionize the detection, prevention and
treatment of conditions from cancer to depression
to old age itself.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
In the foreseeable future, medical doctors will
drip droplets of our genes onto a biochip to
figure out if we have the kind of prostrate
cancer that will kill or not. Scientist will
learn which genes turn on when a wound heal. It
is the letters ATCG on and on for about 3.2
billion of such letters that provides the
information.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
In the eyes of the critic, it threatens to
undermine privacy and brings on genetic
discrimination in insurance and employment. The
Structure of Nucleic Acids The chemistry of DNA
has been studied since 1868 and by 1900 the basic
chemistry of nucleic acids was worked out. By
1920, two forms of nucleic acids were
differentiated
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA and RNA Both deoxyribonucleic acid (DNA) and
ribonucleic acid (RNA) are high-molecular-weight
polymeric compounds. The chain-like
macromolecule is made up of strings of monomeric
units called nucleotides. On complete hydrolysis
nucleic acids yields pyrimidine and purine bases,
a sugar component and phosphoric acid.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Each nucleotide is composed of three components
MONOMERIC COMPONENTS 1. Pentose and Deoxypentose
sugar a cyclic 5 carbon sugar
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• These sugars in polynucleotides occur in
• - Either D-ribose in RNA or
• 2'-deoxyribose in DNA
• Ribose C2 OH
• Deoxyribose C2 H

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NUCLEIC ACIDS STRUCTURE and FUNCTION
2. The Nitrogenous bases, which is either
Pyrimidine or a Purine derivative. The bases are
planar, aromatic, heterocyclic molecules.
Purine Bases
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Pyrimidine bases
The pyrimidine bases are derivatives of the
parent compound pyrimidine and includes
thymine,cytosine and uracil.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The bases, Adenine, Guanine and Cytosine are
found in both DNA and RNA. Thymine is present
only in DNA. Uracil is present only in RNA. In
certain of the bacterial viruses cytosine is
replaced by 5-methylcytosine or
5-hydroxymethylcytosine. Both the purine and
pyrimidine bases can undergo keto-enol
tautomerism
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NUCLEIC ACIDS STRUCTURE and FUNCTION
3. Phosphate group A molecule of Phosphoric
acid, PO43- Nucleosides When a purine or a
pyrimidine base is linked to ribose or
deoxyribose the resulting compound is known as a
nucleoside. The nucleosides from ribose
ribonucleosides The nucleosides from
2-deoxyribose deoxyribonucleosides
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The nucleosides derived from 2-deoxyribose are
known as deoxyadenosine, deoxyguanosine,
deoxycytidine, deoxythymidine etc.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Nucleotides When a purine or a pyrimidine is
linked to ribose or deoxyribose and phosphoric
acid the resulting compound is known as a
nucleotide. Those derived from ribonucleosides
are referred to as ribonucleotides. Those
derived from deoxyribonucleosides are referred to
as deoxyribonucleotides.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Nucleotides Since the ribonucleosides have three
free hydroxyl groups on their sugar ring, three
possible monophosphate can be formed. The ribo
and deoxyribo nucleoside 5'-phosphate may be
further phosphorylated at position 5' to yield
5'-di- and 5'-tri-phosphates. e.g. Adenosine
5'-phosphate (AMP), Adenosine 5'-diphosphate
(ADP), Adenosine 5'-triphosphate (ATP)
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Primary Structure of Nucleic Acids In a
nucleotide, a base is attached to a pentose sugar
by N-glycosidic bonds to carbon 1 of the sugar
and a nitrogen atom of the base. Sugar is
attached at position N-1 of the pyrimidine
base. Sugar is attached at position N-9 of the
purine base.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Primary Structure of Nucleic Acids The
phosphate is attached to the 5' carbon of the
sugar by phosphodiester linkages. The phosphate
is responsible for the strong negative charge of
nucleic acids. Nucleic acids are
polyanions. Chemically, nucleic acids are
composed of covalently linked chains of
nucleotides.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Primary Structure of Nucleic Acids
Linkage between 5'-Phosphate and 3'-OH
group. 3'-5'-internucleotide linkage in both DNA
and RNA was confirmed by Cohn and his colleagues
in 1956.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA base composition In 1952, Chargaff described
fundamental features of DNA The sum of purines
is equal to the sum of pyrimidines. The sum of
the amino bases is equal to the sum of keto
bases. This equivalence of A and T, and G and C
are importance in relation to the formation of
the DNA double helix.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA base composition contd DNA isolated from
different species reveals wide variations in the
molar proportions of bases. This is independent
of the age of the organism, its nutritional state
or any environmental factor. The ratio,
AT/GC, called the base ratio may vary widely
between species, and remains constant for any one
species. These relationships are referred to as
Chargaff's rule
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Molar proportion of bases (as moles of base per
100 moles of phosphate) in DNAs from various
sources.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA base composition contd DNA's base
composition varies widely among different
organism G C ranges from 25 - 75 in different
species of bacteria this is relatively constant
among related species. G C ranges from 39 -
46 in mammals. With RNA these rules do not
apply - ss RNA With ds RNA in certain viruses
the rule would apply
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Molecular Weight of DNA The molecular weight of
DNA ranges from 106 to 1010 daltons. The size of
the DNA molecules is now customarily described in
terms of Kilobase pairs (kb) rather than Daltons
or Molecular weight. A molecular weight of one
million corresponds approx. to 1.5 kb. E.g. E.
coli MW 3 x 109 4500 kb.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary Structure of DNA James Watson and
Francis Crick published in Nature the
3-dimensional structure of the DNA molecule. The
impact of their model has been enormous and it
constitutes as the foundation of modern molecular
biology. Ref. Watson, J.D. and Crick, F.H.C.
(1953) Nature, 171, 373 Ref. Franklin, R. and
Gosling, R. G. (1953) Nature, 171, 740 172,
156. (Crick died Aug. 2004 He was 88 years old)
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary Structure of DNA The study of the
molecular architecture started long before Watson
and Crick, actually by Astbury (1947), and later
by Rosalind Franklin and Gosling (1953). X-ray
diffraction was used to elucidate the secondary
structure of DNA. The diffraction pattern of the
mounted fibre is then recorded in an atmosphere
of controlled humidity.
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• The Secondary Structure of DNA
• Watson and Crick in 1953 proposed that the DNA
  molecule extended chain having a highly ordered
  structure and is composed of
• two complementary polymeric chains twisted about
  each other.
• the two stands run in opposite directions
  (antiparallel alpha-helices), and are of opposite
  polarity.

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NUCLEIC ACIDS STRUCTURE and FUNCTION

• The Secondary Structure of DNA
• the rails of the ladder run in opposite direction
  contain alternating units of deoxyribose sugar
  and phosphate.
• the polynucleotide chain, the sugar and phosphate
  groups are always linked together by 3 - 5
  phosphodiester linkages.
• the purine and pyrimidine bases are flat
  (planar), are relatively water-insoluble and are
  stack tightly on top of one another like a pile
  of plates.

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NUCLEIC ACIDS STRUCTURE and FUNCTION

• The Secondary Structure of DNA
• the bases are arranged at right angles to the
  long axis of the polynucleotide chain.
• each step is composed of a pair of nucleotides.
• the order of the purine and pyrimidine bases
  along the chain is highly irregular.
• the chain is not straight but is wound helically
  around a central axis, one full turn ( the pitch)
  of the helix extending 3.4 nm (34 Å), and there
  are 10 bases per turn.

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NUCLEIC ACIDS STRUCTURE and FUNCTION

• The Secondary Structure of DNA
• the bases are separated by a spacing of 0.34 nm
  (3.4 Å).
• the width of the double helix is approx. 2 nm (20
  Å).
• the chains are complementary, in that the
  sequence of bases on one strand is the exact
  complement of the other strand.

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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary Structure of DNA
This form of the double helix is known as the
B-form. Complementary strand of the opposite
polarity lying below 5'-ACGT-3' 3'-TGCA-5

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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary Structure of DNA
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• The Secondary Structure of DNA
• There are two reasons why the bases must pair in
  this specific way
• The purine, with a double ring are larger
  structures than pyrimidine, with a single ring.
  If two purine are paired their dimensions are
  too great to fit the constant diameter of the
  double helix (2 nm) while the dimensions of the
  two pyrimidine are too small.

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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary Structure of DNA 2.The second
determinant of specificity is the positions on
the bases of the hydrogen atoms that can
participate in bonding.
This is essential to the biological functioning
of DNA. If the hydrogen atoms had no fixed
positions, ade could often pair with cytosine and
gua with thymine. The complementary relationship
between the opposing chain sequences that gives
DNA the capacity for self-replication.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary Structure of DNA Occasionally,
H-atoms do undergo shift to other positions and
when this occurs new pairing interactions may be
possible, this is called tautomeric shifts. The
nitrogen atoms attached to the purine and
pyrimidine rings are usually in the amino (NH2)
form and only rarely assume the imino (NH)
configuration,
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary Structure of DNA Likewise, the
oxygen atoms attached to C6 atoms of guanine and
thymine normally have the keto (C-O) form and
rarely take up the enol (COH) configuration. If
the H-atom normally present at the 6-amino
position in adenine shifts to the N1 position,
Ade will pair with cytosine instead of with
thymine.
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• DNA Conformations
• Wilkins and his colleagues demonstrated that,
  depending on the conditions chosen to produce the
  DNA fibres, they can have a variety of possible
  conformations (structures).
• The major forms are the
• B-form, basically describes the Watson and Crick
  model,
• A-form DNA,
• Z-form DNA.

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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations Structural features of DNA
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations B-form DNA B-form DNA is
thought to represent the conformation of most DNA
found in cells. The main features that
distinguish B-form DNA from other forms are
the pitch, the angle of tilt that the base
pairs make with the helical axis, and the
distinct major and minor grooves. The B-DNA is
long and thin.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations B-form DNA There is a lot of
water associated with DNA. Up to 72 molecules
per 12 base pairs. The hydrogen bonding
potential is much greater in the major groove
than in the minor groove and there appears to be
greater dependence on base sequence for
interaction as it was later shown that proteins
attach to sequence-specific DNA segments.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations B-form DNA
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations A-form DNA The B-DNA is
converted to A-DNA by tilting the base pairs some
30 deg so that successive base pairs occur every
0.28 nm.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations A-form DNA The B-DNA is
converted to A-DNA by tilting the base pairs some
30 deg so that successive base pairs occur every
0.28 nm. The bases are tilted and lie well off
the axis as a result the A-DNA is short and broad
as with deeper and narrow major grooves. This
is the predominant conformation of DNA-RNA
hybrids and double stranded RNA segments.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations Z-form DNA DNA containing
alternating purine and pyrimidine residues
(dinucleotides CGCGCGCG) can fold up into
left-handed as well as right handed helices.
The phosphate in the backbone is zig-zagged due
to the fact that the repeating unit is a
dinucleotide rather than a mononucleotide hence
the name Z-DNA. Z-forms will also form in 1 mM
MgCl2 if the C5 of cytosine is substituted with
methyl, bromo or iodo groups.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations Z-form DNA Z-DNA contains 12
bases per turn, and a pitch of 4.5 nm, and
inclination of base pair from the horizontal 9,
this gives the overall Z-DNA an elongated and
slimmer look. Only very minor amounts of Z-DNA
exists in-vivo, and is probably important
immunologically.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
DNA Conformations Z-form DNA
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Deformation of the double helix The sugar
phosphate backbone causes the double helix to be
quite rigid. Also important in conferring
rigidity is the stacking of the bases.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Deformation of the double helix In solution DNA
is quite a plastic molecule it is constantly
subjected to localized thermally induced
fluctuations in the arrangement of its atoms
which causes individual molecules to bend, twist
and stretch. DNA that tends to kink reveals a
set of four CAAAAAT or CAAAAAAT segments and was
found to be separated by single turns (10-nt) of
the double helix.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
conformation DNA can either be linear or
circular. Most if not all bacterial chromosomes
are circular. Certain phages or viruses have
linear DNA e.g. Lamda phage, adenovirus,
poxvirus. Some molecules that are linear when
isolated from a virus particle are found as
circular forms inside the host.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
conformation DNA is naturally supercoiled and
is biologically very important. Supercoiled
refers to the twisting of the double helical DNA.
DNA is naturally negatively supercoiled. DNA
can be negatively suprecoiled (right handed) or
positively supercoiled (left handed). Negative
Supercoiling results from under-winding or
unwinding, where as positive supercoiling results
from tighter winding.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Protein complexes DNA is always found complexed
with specific DNA binding proteins to form
compact molecules called chromatin. In
eukaryotes, the most prominent DNA binding
proteins are the histones. Histones are
relatively small, positively charged
arginine-lysine rich proteins that aggregate
together, around which DNA supercoils. Bacteria
contain histone-like DNA binding proteins.
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• The Secondary and Tertiary Structure of RNA
• RNA, like DNA is composed of a linear sequence of
  nucleotides.
• The main differences between DNA and RNA is that
• the sugar phosphate backbone contains ribose
  instead of deoxyribose
• 2. contains the base uracil instead of thymine.

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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary and Tertiary Structure of RNA RNA
retains all the information of the DNA sequence
from which it was copied as well as base pairing
properties of DNA. RNA molecules are single
stranded and are very short compared to DNA
molecules since they are copied from a small
region of the DNA. RNA has the capacity to form
double helical regions.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary and Tertiary Structure of RNA The
secondary structure is generally similar to the
A-form of DNA with tilted bases since the 2-OH
hinders B-structure formation. RNA is highly
susceptible to base catalysis hydrolysis and
yields a mixture of 2 and 3- nucleotide because
of the 2-OH. Short triple stranded regions can
occur in RNA in which two chains run parallel
with one another.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary and Tertiary Structure of
RNA Homopolymer chains poly (A) and poly (U)
have been shown to form a triple stranded
structure in which antiparallel poly (A) and poly
(U) are held together by conventional
Watson-Crick base pair and a second poly (U)
strand uses Hoogsteen base pairs to bind in
parallel to the poly (A) strand. There are
three major types of RNA in the cell mRNA, tRNA
and rRNA.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary and Tertiary Structure of
RNA mRNA mRNA is synthesized during the process
of transcription, in which the sequence of bases
in one strand of the DNA is enzymatically
transcribed into the form of a single strand of
mRNA with complementary base sequence. mRNA
differ greatly in molecular weight and in base
sequence total cellular mRNA 5
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary and Tertiary Structure of RNA
tRNA tRNA are relatively small molecules that
act as the carriers of specific amino acids
during protein synthesis. Total cellular tRNA
15
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary and Tertiary Structure of RNA
rRNA rRNA is the most abundant RNA. These are
the site for protein synthesis. Total cellular
rRNA 80.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
The Secondary and Tertiary Structure of RNA In
Eukaryotes mRNA that is made is not as simple as
that for prokaryote. Eukaryotes have mRNA with
coding sequences exons, interrupted by
non-coding sequences called introns. The RNA
is spliced to remove the introns, then the RNA
moves to the cytoplasm as an mRNA molecule that
can now direct the synthesis of a particular
protein.
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• Denaturation and Renaturation of DNA
• The DNA double helix can unwind to form single
  strands when subjected to
• extremes of pH
• 2. increased temperature
• 3. decreased dielectric constant by alcohols,
  ketone, etc.
• 4. exposure to amides or urea

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NUCLEIC ACIDS STRUCTURE and FUNCTION
Denaturation and Renaturation of DNA The DNA is
said to denature and changes from a double helix
to a random coil. During denaturation no
covalent bonds in the backbone structure are
broken. When heat is used as the denaturant the
DNA is said to melt and the temperature at which
the strands separate is the melting or transition
temperature Tm.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Denaturation and Renaturation of DNA The
component bases of a polynucleotide absorb light
at 260 nm but in ds-DNA the absorption is
partially suppressed because of the stacking of
the bases. When the bonds break and the bases
unstack there is an increase in the absorption at
260 nm which rises by about 20-30. This is the
hyperchromic effect and is used to monitor the
melting of DNA.
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• Denaturation and Renaturation of DNA
• The nature of the melting transition is affected
  by 3 factors
• The GC content of the DNA
• 2. The nature of the solvent.
• 3. The nature of the DNA.

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NUCLEIC ACIDS STRUCTURE and FUNCTION
Denaturation and Renaturation of DNA Under
appropriate conditions denatured DNA can easily
re-form double helices in a process called DNA
renaturation or hybridization. Hybridization
can occur between any two single-stranded nucleic
acid chains provided they have a complementary
sequence. DNADNA DNARNA RNARNA. There is
about 20 hybridization between the DNAs of man
and mouse.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Function of Nucleic Acids Understanding the
structure of the DNA molecule gives clues to its
biological function. The Watson and Crick model
matched up to the functional requirement as the
genetic material. Requirements 1. The genetic
material is the blueprint for the cell and
carries the information necessary to direct all
its specific activities.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Function of Nucleic Acids 2. The genetic
material replicates, reproduces itself, so that
the information it carries is inherited in a very
precise way by daughter cells. 3. It can
transfer its information to the protein synthesis
apparatus of a cell by the synthesis of an RNA
molecule. 4. It has great physical and chemical
stability. The presence of the 2 deoxyribose
makes the phosphodiester bonds quite resistant to
hydrolysis.
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• Function of Nucleic Acids
• 5. The genetic material can undergo mutations so
  that the message is altered in a specific
  heritable way. One daughter cell will have
  identical sequence to the parent and the other
  daughter cell will have a slightly different base
  sequence.
• DNA has two main functions
• To direct its own replication during cell
  division
• To direct transcription of complementary
  molecules or RNA

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NUCLEIC ACIDS STRUCTURE and FUNCTION

• Function of Nucleic Acids
• RNA has more varied biological functions
• mRNA formed by DNA transcription, directs
  ribosomal synthesis of polypeptides in a process
  known as translation.
• RNAs of the ribosomes have functional as well as
  structural roles. rRNA is composed of about 2/3
  RNA and 1/3 protein.
• During protein synthesis a.a are delivered to the
  ribosome by molecules of transfer RNA.

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NUCLEIC ACIDS STRUCTURE and FUNCTION
Function of Nucleic Acids 4. Certain RNAs are
associated with specific proteins to form
ribonucleoproteins that participate in
post-transcriptional processing of other
RNAs. 5. In many viruses, RNA, and not DNA is
the carrier of genetic information. Crick's
Central Dogma (Theme) Stated that genetic
information stored in the DNA flows through RNA
to proteins.
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• Crick's Central Dogma (Theme)
• Assumptions
• Information flow is one-way (unidirectional)
• ?Only DNA is a template that can be replicated
• ?Working catalysts are proteins
• ?Translation of the information is from the DNA
• ?DNA is the ultimate molecule that encodes the
  genetic information

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NUCLEIC ACIDS STRUCTURE and FUNCTION
Crick's Central Dogma (Theme) Studies of viruses
show that the RNA, like DNA, can store and
transmit genetic information. In 1970 with the
discovery of reverse transcriptase, and RNA virus
encoding protein catalyst (enzyme), showed that
genetic information flows is two-way between DNA
and RNA. In the 1980s it was discovered that
RNA had other remarkable functions.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Crick's Central Dogma (Theme) RNA molecules had
catalytic properties. Cech showed that RNA
intron catalyses its own self-splicing without
the aid of any protein group 1 intron in RNA.
Altman characterised an enzyme from E. coli,
called RNase P that trimmed the 5-end of t-RNA
precursors. Since this discovery, 7 naturally
occurring classes of ribozymes have been
recognised.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Crick's Central Dogma (Theme) Due to the
different chemistry of RNA, having ribose rather
than deoxyribose might give it enzymatic
properties that would permit it to catalyse its
own self replication. RNAs informational
template and catalytic abilities lead to the
hypothesis that RNA evolved before the appearance
of DNA or protein. RNA degrades and mutate much
more easily than DNA molecules.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
RNA as the evolutionary molecule RNA was
proposed to be the first molecule and that the
first forms of life were probably entirely RNA
based and originated 4 billion years ago. The
coding, template and catalytic abilities of RNA
lead to the expanded formulation of the central
dogma and support the hypothesis that RNA was the
first biological molecule. DNA cannot assemble
itself it requires proteins to do so.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
RNA as the evolutionary molecule In the absence
of selective pressure to change the system there
will be many imprints of the evolutionary
past. RNA is found in diverse cellular locations
from the nucleus outward, carrying out a variety
of new functions. Since RNA is central to life,
many RNA carry vestiges of those early RNA
structures and functions.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
Support of evolutionary role RNA has both
informational and catalytic functions, no other
molecules has such function. The nt sequences of
RNA common to all organisms, e.g. rRNA. They are
highly conserved among different species. RNA is
involved in most critical cellular functions
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NUCLEIC ACIDS STRUCTURE and FUNCTION

• Support of evolutionary role
• Functions include
• ATP, universal energy carrier
• ?Protein synthesis, mRNA, t-RNA, rRNA
• ?rRNA by itself catalyses peptide bond formation
• ?Uracil, found in RNA is the precursor of thymine
  in DNA
• ?RNA is the primer of DNA replication
• Small RNAs (snRNA) are involved in the processing
  of mRNA

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NUCLEIC ACIDS STRUCTURE and FUNCTION
RNA, Health and Disease Many viruses have RNA
genomes e.g. human pathogens polio, HIV, flu,
measles, plant pathogens potyviruses. It is
difficult to control RNA viruses because of their
high mutation rates (10-3 to 10-4 per base pair
per replication). Viruses replicate millions of
times per day so random mutations are constantly
occurring.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
RNA, Health and Disease In the case of HIV, it
is estimated that each of the 10,000 RNA bases is
mutated more than 10,000 times each day in an
infected person. In similar ways, new strains
of cold and flu viruses continue to
emerge. Evolutionary considerations therefore
will dictate the ways drugs are administered, as
this is a key factor in their long term
effectiveness.
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NUCLEIC ACIDS STRUCTURE and FUNCTION
RNA, Health and Disease The strategy therefore
uses several drugs that hit different steps of
the viral reproduction cycle cocktail. Current
treatment for HIV e.g. employs drugs such as
acyclovir, AZT, and protease inhibitors, each
targeting different aspects of viral
replication. A new strategy focussing on RNA
with potential against viral pathogens is
currently being explored in the laboratory One
such strategy is called antisense technology .
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NUCLEIC ACIDS STRUCTURE and FUNCTION
RNA, Health and Disease The strategy is to
engineer into the affected cells a antisense copy
of the defective gene, i.e., one in which the
5-3 orientation of the gene has been reversed
relative to its promoter. The antisense
transcripts are now complementary to the sense
transcripts from the defective gene. Antisense
and sense RNA molecules can now bind to one
another, effectively silencing the expression of
the defective target gene a term now referred to
as gene silencing