College of Education Salahaddin University Kirkuk Road ErbilIraq Tel 07504095454 Research Fellow Manchester Fungal Infection Group The University of Manchester Institute ID: 933987
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Slide1
Molecular Biology
Medical BiologistCollege of Education Salahaddin UniversityKirkuk Road Erbil-Iraq Tel.: 07504095454
Research Fellow Manchester Fungal Infection Group The University of Manchester Institute of Inflammation and Repair Manchester, UK M13 9NTTel. 07927133678
GBD Expert Global Burden of Disease IHME Institute for Health Metrics and Evaluation University of WashingtonSeattle, WA 98121, USA
Dr
Karzan Mohammad
PhD
. MSc. BSc.
Slide2Definition
DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA.
Slide3DNA - a polymer of
deoxyribo nucleotidesfound in chromosomes, mitochondria and chloroplasts
carries the genetic information
Slide4Does
DNA fit the requirements of a hereditary material?Structure
REQUIREMENT
DNA Component
Has biologically useful
information to make protein
Genetic code:
3 bases code for 1 amino acid(protein)
Must reproduce faithfully and transmit to offspring
Complementary bases are faithful: found in germ cells
Must be stable within a living organism
Backbone is strong covalent : hydrogen bonds
Must be capable of incorporating stable changes
Bases can change
through known
mechanisms
Slide5Structural Components
DNA has three main components1. deoxyribose (a pentose sugar)2. base (there are four different ones)3. phosphate
Slide6Structure
Basic structure of DNA is a sugar-phosphate backbone with
4 variable nitrogenous bases. This structure is called a nucleotide.
P
sugar
Nitrogen base
Phosphate molecule:
HYDROPHILIC
5-carbon sugar:
DEOXYRIBOSE
Nitrogen base:
HYDROPHOBIC
BACKBONE
BASE
Slide7Nucleotide
Nucleoside
Base
Phosphate
Sugar
X=H:
DNA
X=OH:
RNA
Slide8Structure of DNA (primary, Secondary and Tertiary)
Based on Complexicity. The primary structure = nucleotide structure and how the nucleotides are joined together. The secondary structure = stable three-dimensional configuration, the helical structure worked out by Watson and Crick.
DNA’s tertiary structures, = the complex packing arrangements of double stranded DNA in chromosomes.
Slide9Pentose
This minor chemical difference is recognized by all the cellular enzymes that interact with DNA or RNA, thus yielding specific functions for each nucleic acid. Further, the additional oxygen atom in the RNA nucleotide makes it more reactive and less chemically stable than DNA. For this reason, DNA is better suited to serve as the long-term repository of genetic information.
Slide10The Nitrogen Bases
They are divided into two groupsPyrimidines and purines
Pyrimidines (made of one 6 member ring)ThymineCytosinePurines (made of a 6 member ring, fused to a 5 member ring)
AdenineGuanineThe rings are not only made of carbon
Slide11Slide12phosphate group
Consists of a phosphorus atom bonded to four oxygen atoms. Phosphate groups are found in every nucleotide and frequently carry a negative charge, which makes DNA acidic. The phosphate is always bonded to the 5`-carbon atom of the sugar in a nucleotide.
Slide13DNA
Double Helix and Hydrogen BondingMade of two strands of nucleotides that are joined together by hydrogen bondingHydrogen bonding occurs as a result of complimentary base pairingAdenine and thymine pair upCytosine and guanine pair upEach pair is connected through hydrogen bonding
Hydrogen bonding always occurs between one pyrimidine and one purine
Slide14Complimentary base pairing of pyrimidines and purines
DNA
Double Helix and Hydrogen Bonding
Slide15DNA
Double Helix and Hydrogen Bonding
Slide16A === T
C === G
DNA
Double Helix and Hydrogen Bonding
An important characteristic of the polynucleotide strand is its direction, or polarity. At one end of the strand a phosphate group is attached only to the 5`-carbon atom of the sugar in the nucleotide. This end of the strand is therefore referred to as the
5
`
end.
The other end of the strand, referred to as the
3
`
end,
has an OH group attached to the 3`-carbon atom of the sugar
Slide17The ‘backbones’ of DNA molecules are made of alternating sugar and phosphates
The ‘rungs on the ladder’ are made of bases that are hydrogen bonded to each otherDNA Double Helix
Slide18Francis Crick and James Watson with Maurice Wilkins received the
1962 Nobel Prize
for discovering the molecular structure of deoxyribonucleic acid (DNA). Widely regarded as one of the most important discoveries of the 20th century it has led the way to the mapping and deciphering of all the genes in the human chromosomes
Slide19Watson and Crick Model:
The sides of the ladder are made up of alternating molecules of phosphate and deoxyribose.
The bases make up the rungs of the ladder are attracted by a weak chemical bonds called hydrogen bonds.
The
DNA double helix is anti-parallel, which means that the 5' end of one strand is paired with the 3' end of its complementary strand (and vice versa).
5
'--------------->3‘
3
'<---------------5'
Two
hydrogen bonds connect T to A; three hydrogen bonds
connect
G to C
.
Slide20Different forms of DNA double helix
A-DNA
B-DNAZ-DNA
Slide21A-DNA
A-DNA is one of the many possible double helical structures of DNA. It is most active along with other forms.
Helix has left-handed sense, shorter more compact
helical structure
.
I
t
occurs only
in dehydrated samples of DNA
, such as those used
in crystallographic experiments.
The A-DNA structure.
Slide22Structure
A-DNA is fairly similar to
B-DNA.Slight increase in the number of bp/ rotation (resulting in a tighter rotation angle), and smaller rise/turn
. deep major groove and a shallow minor groove.
Favoured
conformation at
low water
concentrations
.
In a solution with higher salt concentrations or with alcohol added, the DNA structure may change to an
A form
, which is still right-handed, but every
2.3 nm makes a turn
and there are
11 base pairs per turn.
Slide23FunctionA transition from B-DNA to A-DNA occurs during Transcription.
A-DNA also plays a imp role in some processes that do not involve RNA.For Example: In sporulating bacteria, there is a protein which can bind to DNA in the B-conformation & induce a change to the A-DNA helix
Also, Long terminal repeats (LTRs) of transposable elements, these regions often contains purine stretches which favour the A-DNA conformation.
Slide24B-DNA
Most
common DNA conformation in vivo.Favoured conformation at
high water concentrations.Also known as
Watson & Crick model
of DNA.
First identified in fibre at 92% relative humidity.
The
B-DNA
structure
Slide25StructureNarrower, more elongated helix than A.
Wide major groove easily accessible to proteins & Narrow minor groove. Base pairs nearly perpendicular to helix axis
One spiral is 3.4nm or 34Ǻ.
Distance between two
H-bonds
is 0.34nm or 3.4Ǻ.
Slide26Z-DNAZ-DNA
is one of the many possible double helical structures of DNA.Helix has left-handed
sense. It is most active double helical structure.Can be formed
in
vivo
,
given proper sequence and
super helical
tension, but function remains obscure.
The Z-DNA structure.
Slide27Z-DNA is a
transient form of DNA.
Narrower, more elongated helix than A or B.
Z-DNA was first discovered in 1979,certain proteins bind very strongly to Z-DNA.
Z-DNA
plays an important biological role in protection against
viral
disease
.
One turn spans 4.6 nm, comprising
12
base
pairs
.
The DNA molecule with alternating G-C sequences in alcohol or high salt solution tends to have such structure.
Structure
Slide28Function
While
no definitive biological significance of Z-DNA has been found, it is commonly believed to provide torsional strain relief (supercoiling) while DNA transcription occurs.
Toxic effect of ethidium bromide on t
trypanosoma
is caused by shift of their
kinetoplastid
DNA
to Z-form.
Scientists have since discovered that certain proteins bind very strongly to Z-DNA, suggesting that Z-DNA plays an important biological role in protection against
viral
disease
.
Slide29Direction of Helix
Slide30The helix axis of A-, B-, and Z-DNA.
Helix sense
: Right-handed
Right-handed
Left-handed
Bp
/turn
:
11
10
12
Diameter :
23Ǻ
20Ǻ
18Ǻ
Axial rise(nm) :
0.26 0.34
0.45
Slide31Factors involved for different DNA conformations
:There are at least three factors on which the DNA conformation depends
Ionic or hydration environment DNA sequences.Presence of specific proteins
In a living cell, DNA is a Mixture of A-& B-DNA conformation with a few regions capable of forming Z-DNA
Slide32Slide33