Concept of DNA

8/3/2019 Concept of DNA

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Concept of DNA

Dr. rer. nat. Anto Budiharjo, S.Si., M.Biotech\


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Why study nucleic acids?

DNA is the focus of attention because of its role in

carrying and expressing genetic information.

The Human Genome Projectwhere 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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Important Scientists that determined

DNAs Importance

Frederick Griffith : bacterial transformation

Oswald Avery : DNA key to transformation Alfred Hershey & Martha Chase :

Bacteriophage transformation experiment

Erwin Chargaff : base-pairing rules


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Important Scientists in the Race for

the Double Helix

Maurice Wilkins & Rosalind Franklin

X-ray diffraction

DNA must be a some type of spiral (helix)

DNAs diameter is constant and stable

James Watson & Francis Crick

Created the first accurate model of DNA

Won the Nobel Prize


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The structure of nucleic acids

The chemistry of DNA has been studied

since 1868 and by 1900 the basic

chemistry of nucleic acids was workedout.

By 1920, two forms of nucleic acids weredifferentiated: DNA & RNA


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DNA & 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 callednucleotides.


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Nucleotide Nucleocide


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Each nucleotide is composed of three

components: MONOMERICCOMPONENTS

1. Pentose and Deoxypentose sugar: a cyclic 5 carbon

sugar

These sugars in polynucleotides occur inEither D-ribose in RNA or

2'-deoxyribose in DNA

Ribose C2 = OHDeoxyribose C2 = H


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Deoxyribose C2 = H Ribose C2 = OH


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2. The Nitrogenous bases, which is either

Pyrimidine or a Purine derivative. The bases

are planar, aromatic, heterocyclic molecules.


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3. Phosphate group

A molecule of Phosphoric acid, PO43-

Nucleosides

When a purine or a pyrimidine base is linked toribose or deoxyribose the resulting compound isknown as a nucleoside.

The nucleosides from ribose = ribonucleosides

The nucleosides from 2-deoxyribose =deoxyribonucleosides


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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 thebase.

Sugar is attached at position N-1 of thepyrimidine base.

Sugar is attached at position N-9 of the purinebase.


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The Primary Structure of Nucleic Acids

The phosphate is attached to the 5' carbon of thesugar by phosphodiester linkages.

The phosphate is responsible for the strong

negative charge of nucleic acids.

Nucleic acids are polyanions.

Chemically, nucleic acids are composed ofcovalently linked chains of nucleotides.


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Primary Structure of Nucleic Acids

Nucleotides are bound

together to form nucleic

acids.

The sequence of bases is

like an instruction

manual that can be read

by the cell.


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Genetic Diversity

Different arrangementsof NUCLEOTIDES in a

nucleic acid (DNA)

provides the key to

DIVERSITY among livingorganisms.


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Secondary Structure of

Nucleic Acids

DNA:

The Double Helix

The vertical blue strand represents

the sugar and phosphate group

and the inner horizontal bands

represent the nitrogenous bases


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Nucleic Acids

DNA:

The Double Helix

Complementary base

pairs

Helical


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Nucleic Acids

RNA:

Single stranded, but loopy in structure


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DNA base composition

In 1952, Chargaff described fundamental featuresof DNA:

The sum of purines is equal to the sum ofpyrimidines.

The sum of the amino bases is equal to the sumof keto bases.

This equivalence of A and T, and G and C areimportance in relation to the formation of theDNA double helix.


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DNA isolated from different species reveals widevariations in the molar proportions of bases.

This is independent of the age of the organism,its nutritional state or any environmental factor.

The ratio, A+T/G+C, called the base ratio mayvary widely between species, and remainsconstant for any one species.

These relationships are referred to as Chargaff'srule


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Molar proportion of bases (as moles of base per 100 moles of

phosphate) in DNAs from various sources.


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Watson and Crick in 1953 proposed that the DNAmolecule extended chain having a highly ordered

structure and is composed of:

two complementary polymeric chains twistedabout each other.

the two stands run in opposite directions(antiparallel alpha-helices), and are of oppositepolarity.

the rails of the ladder run in opposite direction

contain alternating units of deoxyribose sugarand phosphate.

the polynucleotide chain, the sugar andphosphate groups are always linked together by

3 - 5 phosphodiester linkages.


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There are two reasons why the basesmust pair in this specific way:

1. The purine, with a double ring are largerstructures than pyrimidine, with a single ring. Iftwo purine are paired their dimensions are too

great to fit the constant diameter of the doublehelix (2 nm) while the dimensions of the twopyrimidine are too small.

2. The second determinant of specificity is thepositions on the bases of the hydrogen atomsthat can participate in bonding.


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How to write

DNA sequence


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DNA conformation

Wilkins and his colleagues demonstrated that,depending on the conditions chosen to produce theDNA fibres, they can have a variety of possibleconformations (structures).

The major forms are the:

1. B-form, basically describes the Watson and Crick

model,2. A-form DNA,

3. Z-form DNA.


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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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DNA can either be linear or circular

Most if not all bacterial chromosomes arecircular.

Certain phages or viruses have linear DNAe.g. Lamda phage, adenovirus, poxvirus.

Some molecules that are linear whenisolated from a virus particle are found ascircular forms inside the host.


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DNA is naturally supercoiled and is biologicallyvery important. Supercoiled refers to the twisting

of the double helical DNA. DNA is naturallynegatively supercoiled.

DNA can be negatively suprecoiled (right handed)or positively supercoiled (left handed).

Negative Supercoiling results from under-winding

or unwinding, where as positive supercoilingresults from tighter winding.


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DNA is always found complexed with specific DNAbinding proteins to form compact molecules

called chromatin.

In eukaryotes, the most prominent DNA binding

proteins are the histones.

Histones are relatively small, positively chargedarginine-lysine rich proteins that aggregate

together, around which DNA supercoils. Bacteriacontain histone-like DNA binding proteins.

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Concept of DNA