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DNA

DNA acts as a genetic  Fredrick Griffith’s – experiment


material  Oswald Avery, MacLeod CM, and
McCarty M – experiment
 Alfred Hershey & Martha Chase
– experiment
The presence of heat-killed S cells transforms live R
cells into live S cells.
(d) Mouse dies after injection with a mixture of heat-killed S
strain and live R strain. The heat-killed S strain somehow
DNA is the agent transforming the R strain into virulence. If
the DNA in an extract of heat-killed S strain cells is destroyed, then
mice injected with a mixture of the heat-killed cells and the live non-
virulent strain R are no longer killed
The Hershey–Chase experiment demonstrated that the
genetic material of phage is DNA, not protein. The experiment
uses two sets of T2 bacteriophage. In one set, the protein coat is
labeled with radioactive sulfur (S35), not found in DNA. In the other
set, the DNA is labeled with radioactive phosphorus (P32), not found in
DNA

 DNA acts as a genetic  Fredrick Griffith’s – experiment


material  Oswald Avery, MacLeod CM, and
McCarty M – experiment
 Alfred Hershey & Martha Chase
– experiment

What is the advantage of DNA being a genetic materi


Structure of DNA

*Chargaff’s rule*

*Chemical composition *X-ray diffraction data*


of DNA*

DNA is a double helix composed of two strands of linked nucleotides


that wind around each other

-Watson & Crick


1. Building blocks of DNA
Phosphodiester bonds are backbone of DNA chain

The backbone of DNA


and RNA are
hydrophilic. The
hydroxyl group of sugar
residues form hydrogen
bonds with water.
The phosphate groups
are completely ionized
and negatively charged
at physiological pH and
the negative charges
are neutralized by ionic
interactions with
Properties of nucleotides

Adenine Guanine

Cytosine Uracil Thymine

Nitrogenous bases common in DNA and RNA are highly


conjugated molecules, a property with important consequences
for the structure, electron distribution, and light absorption of
nucleic acids.
Tautomeric bases of nucleic acids

keto – enol tautomers amino - imino tautomers


Nucleic acids has absorption maxima at λ260

Absorption spectra of the common nucleotides. The


spectra are shown as the variation in molar extinction
coefficient with wavelength. The molar extinction coefficients
at 260 nm and pH 7.0. For mixtures of nucleotides, a
wavelength of 260 nm is used for absorption measurements.
Structural properties of nucleotides in nucleic acids

C2’-Endo
PO

7.0 Ao
PO

C3’-Endo
PO

5.9 Ao
PO

Sugar molecules are not planar due


to a number of unfavourable
interactions. To alleviate this, one
The limited rotation about bond 4 or two of the atoms twist out of the
gives rise to ring pucker, in which plane and exist in four different
one of the atoms in the five- puckered conformation. In all cases,
membered furanose ring is out of four of the five atoms are in a
the plane described by the other single plane. The fifth atom (C2’ or
four to avoid steric hinderance. C3’) is on either the same (endo) or
C3 – endo C2 – endo
Glycosidic conformations of purines and pyrimidine

8
H
6
H

In pyrimidines, steric clashes between the sugar and O 2 (linked


with C2) of the base strongly disfavors syn conformation. In
purines anti and syn conformations rapidly interconvert, with
anti being more stable in most cases. The syn conformation is
stabilized in guanosine because of favourable interaction
between the 2-NH2 group and the phosphate oxygens.
2. Chargaff’s rule

1. The total amount of pyrimidine nucleotides (T+C) always


equals the total amount of purine nucleotides (A+G)
2. The amount of T always equals the amount of A, and the
amount of C always equals the amount of G. But the
amount of A+T is not necessarily equal to the amount of
G+C. This ratio varies among different organisms but is
virtually the same in different tissues of the same organism.
3. X-ray diffraction analysis of DNA

34 Ao

3.4 Ao

The spots forming a cross in the centre denote a


helical structure. The heavy bands at the left and right
arise from the recurring bases.
Stacking interactions and hydrogen bonding
Residues exposed at the grooves
Stability of sugar – phosphate backbone in DNA

Hydrolysis of RNA under alkaline conditions. The 2’


hydroxyl acts as a nucleophile in an intramolecular
displacement. The 2’,3’-cyclic monophosphate derivative is
further hydrolyzed to a mixture of 2’- and 3’-monophosphates.
DNA, which lacks 2 hydroxyls, is stable under similar
Model of stacking interactions
Denaturation of dsDNA
Noncanonical DNA structures
Anticancer drug Cisplatin change the shape of DNA
Photochemical damage change shape of DNA
Cruciform DNA
Triple Helices
Watson crick base pairing

Hoogsteen base pairing

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