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Presented by: Kathryn Macy Ong, DMD

DNA and RNA

Kathryn Macy Ong, DMD

Nucleic Acids
Storage and
expression of
genetic
information.
Two chemically
distinct types of
nucleic acids:

A. Deoxyribonucleic

Acid (DNA)
B. Ribonucleic Acid
(RNA)
Kathryn Macy Ong, DMD

Deoxyribonucleic Acid
(DNA)

Repository of genetic information


Seen in the nucleus of eukaryotic organisms,
mitochondria and the chloroplasts of plants.
Replication : Genetic information in DNA copied and
transmitted to daughter
Must be able to replicate precisely each time a cell
divides and have the information that it contains
be selectively expressed.
Exists as a doublestranded molecule Double
Helix
Two strands wind around each other
Associated with various types of proteins
Nucleoprotein
Present in
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Ong, DMD
theMacy
nucleus

DNA Structure
A.3'5'-Phosphodiester bonds
Join the 3'-hydroxyl group of the deoxy pentose of one nucleotide
to the 5'-hydroxyl group an adjacent nucleotide through a
phosphate group
Result: Long unchained chain that is not attached to other
nucleotides
5'-end (end with the free phosphate)
3'-end (end with the free hydroxyl)

Bases located along the resulting deoxy ribosephosphate

backbone are always written in sequence from the 5'-end of the


chain to the 3'-end
Can be cleaved hydrolytically by chemicals (alkali for RNA)
enzymatically by a family of nucleases:
Deoxyribonucleases for DNA
Ribonucleases for RNA.
Kathryn Macy Ong, DMD

Kathryn Macy Ong, DMD

DNA Structure
B.Double

Helix

Two chains are coiled around a common axis

Axis of Symmetry
Outside : Hydrophilic deoxyribosephosphate
backbone
Inside: hydrophobic bases

Chains are paired in an anti parallel manner


5'-end of one strand is paired with the 3'-end of the
other strand
Creates a major (wide) groove and a minor

(narrow) groove.
Provide access for the binding of regulatory
proteins to their specific recognition sequences
along the DNA chain
Narrow groove: Anticancer drugs exert cytotoxic
effect to interfere with DNA and RNA synthesis
Kathryn Macy Ong, DMD

DNA Structure: Double


Helix
i.Base pairing:
Bases of one strand of DNA are paired with the bases of

the second strand


Adenine = Thymine
Cytosine = Guanine
Base pairs perpendicular to the axis

Chargaff Rule:
Amount of adenine equals the amount of thymine, the amount
of guanine equals the amount of cytosine
Total amount of purines equals the total amount of pyrimidines
Held together by hydrogen bonds :
Stabilization of the double helix
2 A and T
3 G and C
Kathryn Macy Ong, DMD

Kathryn Macy Ong, DMD

DNA Structure: Double


Helix
ii.Separation

of the two DNA strands in the


double helix
Disruption can occur if the pH of a DNA solution is

altered so that the nucleotide bases ionize, or if


the solution is heated.
When DNA is heated, the temperature at which
one half of the helical structure is lost is
Melting Temperature (Tm).
Loss of helical structure in DNA Denaturation
DNA that contains high concentrations of A and T
denatures at a lower temperature than G- and C-rich DNA
Complementary DNA strands can reform the double helix
Renaturation
or Ong,
Reannealing
Kathryn Macy
DMD

DNA Structure: Double


Helix
ii. Structural

forms of the double helix

B form

Described by Watson and Crick in 1953


Right-handed helix with ten residues per 360 turn of the helix
Bases perpendicular to the helical axis
Primary forms in chromosomal DNA
form
Produced by moderately dehydrating the B form
Also a right-handed helix, but there are 11 base pairs per turn
Planes of the base pairs are tilted 20 away from the perpendicular to the
helical axis
Ex. DNA RNA hybrids or RNA RNA double stranded regions
form
Left-handed helix
Contains about 12 base pairs per turn
Deoxyribose phosphate backbone zigzags ~ Z DNA
Occurs naturally in regions of DNA that have a sequence of alternating
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purines and pyrimidines

** Transitions between the B and Z helical forms of DNA plays a role in regulating gene
expression.
Kathryn Macy Ong,
DMD

C.Linear

and circular DNA molecules

Each chromosome contains one long linear molecule of

dsDNA, bound to a complex mixture of proteins (histone


and non-histone to form chromatin.
Eukaryotes
Closed, circular DNA molecules in the mitochondria

Prokaryotes
Single, double-stranded, supercoiled, circular chromosome
Associated with non-histone proteins that can condense the DNA to
form a nucleoid.
Plasmids
Small, circular, extrachromosomal DNA molecules
Carries genetic information (ex. antibiotic resistance) and undergoes replication

Kathryn Macy Ong, DMD

Ribonucleic Acid (RNA)


Unbranched

polymeric molecules composed of nucleoside


monophosphates joined together by phosphodiester bonds
Differs from DNA:
Smaller than DNA
Contain ribose instead of deoxyribose
Has Uracil instead of Thymine
Single stranded (capable of folding into complex structures)

copying process wherein a DNA strand serves


as a template for the synthesis of RNA

Transcription

a.Ribosomal RNAs
b.Transfer RNAs
c.Messenger RNAs that are translated into sequences of amino

acids
d.Noncoding RNAs
.The three major types of RNA also differ from each other in size,
function, and special structural modifications
Kathryn Macy Ong, DMD

Kathryn Macy Ong, DMD

RNA Structure
A.Ribosomal RNA
Found in association with several

proteins as components of the


ribosomes
Serve as the sites for protein synthesis

Size species of rRNA


Prokaryotic Cells (23S, 16S, and 5S)
Eukaryotic Cytosol (28S, 18S, 5.8S,and 5S).
[S is the Svedberg unit, which is related to
the molecular weight and shape of the
compound.]
Make up about 80% of the total RNA in

the cell.
Ribozyme RNA with catalytic activity
Kathryn Macy Ong, DMD

B.Transfer RNA
Smallest (4S) of the three major types of

RNA
Make up about 15% of the total RNA in
the cell
One specific type of tRNA molecule for
each of the common 20 amino acids
Contain a high percentage of unusual
bases and have extensive intrachain
base-pairing that leads to characteristic
secondary and tertiary structure.
Serves an adaptor molecule that
carries its specific amino acid to the site
of protein synthesis
Covalently attached to its 3'-end
Genetic code sequence on an mRNA is
recognized -- Specifying the addition of amino
acid to the growing peptide chain
Kathryn Macy Ong, DMD

C.Messenger RNA
Comprises only about 5% of the RNA in the

cell,
Most heterogeneous type of RNA in size
and base sequence
Carry genetic information from the nuclear
DNA to the cytosol
Used as the template for protein synthesis. If the
Polycistronic mRNA carries information
from more than one gene
Monocistronic mRNA carries information
from just one gene

Contains untranslated regions at its 5'- and

3'-ends
Special structural characteristics of
eukaryotic mRNA:
poly-A tail long sequence of adenine
nucleotides on the 3'-end
cap 5'-end consisting of a molecule of 7methylguanosine attached backward (5'5)
through a triphosphate linkage
Kathryn Macy Ong, DMD

Genetic Code
Dictionary

that identifies the correspondence between


a sequence of nucleotide bases and a sequence of
amino acids
Each code is composed of three nucleotide bases
Codons
presented in the mRNA language of
Adenine (A)
Guanine (G)
Cytosine (C)
Uracil (U)
Nucleotide sequences are always written from the 5'-end to

the 3'-end.
The four nucleotide bases are used to produce the three-base
codons 64 different combinations of bases
Kathryn Macy Ong, DMD

START Codon
AUG Methionine
Initiates translation
STOP Codons
UAG, UGA, and UAA
When one of these codons appears in an mRNA sequence, synthesis of the
polypeptide coded for by that mRNA stops
Kathryn Macy Ong, DMD

4 Forms of Protein structure


1. Primary structure
Amino acids joined by peptide bonds form a linear

polypeptide chain

2. Secondary structure
Polypeptide chains form sheets and coils

3. Tertiary structure
Sheets and coils pack into functional domains

4. Quaternary structure
Many proteins (e.g. enzymes) consist of two or more chains
Kathryn Macy Ong, DMD

PRIMARY STRUCTURE

Kathryn Macy Ong, DMD

SECONDARY STRUCTURE

Kathryn Macy Ong, DMD

TERTIARY STRUCTURE

Kathryn Macy Ong, DMD

QUATERNARY
STRUCTURE

Kathryn Macy Ong, DMD

IMPORTANCE OF
STRUCTURES
Protein

structure dictates function

Sometimes

a mutation in DNA
results in an amino acid substitution
that alters a proteins structure and
compromises its function
Example:

Hemoglobin

anemia
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and

sickle-cell

NORMAL HEMOGLOBIN
STRUCTURE

Kathryn Macy Ong, DMD

VALINE HISTIDINE LEUCINE THREONINE PROLINE

One amino acid substitution results in the


abnormal beta chain in HbS molecules.
Instead of glutamate, valine was added at the
sixth position of the polypeptide chain.
Glutamate has an overall negative charge;
valine has no net charge. At low oxygen
levels, this difference gives rise to a waterrepellent, sticky patch on HbS molecules. They
stick together because of that patch, forming
rod shaped clumps that distort normally
Kathryn
Macy
Ong, DMD
rounded red blood cells
into
sickle
shapes.

VALINEGLUTAMATE

DENATURATION OF
PROTEINS
Caused

by shifts in pH or
temperature, or exposure to
detergent or salts
Disrupts hydrogen bonds and other

molecular interactions responsible for


proteins shape
If

a protein unfolds and loses its


three-dimensional shape
(denatures), it also loses its function
Kathryn Macy Ong, DMD

References:
Lippincotts Illustrated Reviews: Biochemistry, 5th Ed.
Thomson Brooks/Cole, Biology, 8th Ed.

End

Kathryn Macy Ong, DMD

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