DNA STRUCTURE

ILO : At the end of lectures on this topic, I MBBS students should be able to:
Describe the Structure of DNA

CASE CONNECTION
In a delivery suite, the mother exclaims that her child has some of her features and some of his
father’s.” “Why is it so she asks you?” she asks you what will you say about whose features the
baby can inherit? Consider your answer as you read further.
How Is DNA Structured?
Watson and Crick first described the structure of DNA,( Fig 1) (Noble Prize 1962) our
understanding of how gene is expression ( gene expression means converting a gene ( part of DNA
) to protein) how expression is regulated has increased dramatically, to fully appreciate these
mechanisms you must first understand this structure of DNA .
A deoxyribonucleic acid (DNA) molecule is a polymer of nucleotides. Nucleotides are molecules
that include a phosphate group and a nitrogenous base attached to a pentose sugar.

(Note, the term nucleoside refers to a nitrogenous base attached to a pentose sugar; when a phosphate
group is added, it becomes a nucleotide.)
Phosphodiester bonds link nucleotides together by connecting the 5’ carbon of one nucleotide and
the 3’ carbon of the next (Fig 2, 3). This pattern of bonding creates a 5’ end and 3’ end of each DNA
strand.
DNA absorbs UV ( around 260nm ) light due to heterocyclic rings of the nucleotides, its sugar-
phosphate backbone does not contribute to this absorption.This property is used in DNA estimation.,
 Fig 2 Fig 1

How are 2 stands linked?

DNA molecules involve two strands that
pair with one another according to their
nucleotide sequences. Nucleotides pair
with each other via hydrogen bonds;
3’5’ adenine always pairs with thymine
(denoted A-T) and guanine always pairs
with cytosine (G-C). The term
complementary is often used to describe
Fig 3
this pairing convention (Figure 3).

G-C pairs have three hydrogen bonds while A-T pairs have two. This is why stretches of DNA that
are rich in G-C pairs are more strongly bonded together. The temperature required to separate the
strands (the melting temperature) is higher when more G-C base pair are present.

Complementary DNA strands are oriented in an antiparallel fashion, meaning the 3’ end of one
strand pairs with the 5’ end of the complementary strand.(Fig 3)

The exposed phosphate backbones of each strand give DNA helices an overall negative charge.
The natural configuration of DNA creates a major and minor groove within the DNA helix; these
are important features because various proteins use the two grooves for processes such as
transcription and replication. ( Fig 4)
DNA bends if negative charges of DNA backbone phosphates are NEUTRLISED. An important component
of protein–DNA recognition.
 DNA helices spiral in “right-handed”
orientation, with a single turn of the helix
requiring 10 base pairs. Other structural
orientations of DNA helices have been
described, such as left-handed spirals, but these
rarely occur naturally.
DNA is highly organized:
The human genome contains roughly 3 billion
base pairs, which when fully stretched out is
roughly 2-3 m long. Considering that the
Fig 4
average diameter of a eukaryotic nucleus is 6
µm, you can see why DNA has to be condensed
to a manageable size. This is accomplished by DNA helices winding into highly condensed
structures (Figure 5).
The first step in the winding of DNA
involves proteins called histones.
Histones contain positively charged
amino acids (ie, lysine and arginine) that
bind tightly to the negatively charged
phosphate groups within DNA helices.
DNA winds twice( around 146 base
pairs ) around a core of eight histone
subunits .A ninth histone subunit (H1-
Fig 5 Linker Histone) Coiling around histones
called nucleosomes. Nucleosomes wind
around themselves to organize like 30
mm fibers that contain non histone proteins & some RNA molecules .
Coiled DNA associated with histones, is called chromatin. Chromatin can be further condensed by
supercoiling.
Euchromatin: When chromatin is less condensed, it is referred to as euchromatin it has
transcriptionally active genes
Heterochromatin: When DNA is highly condensed, it is referred to as heterochromatin.
Heterochromatin is transcriptionally inactive.
Introns and Exons :Segment of gene coding for protein is called exon , Unexpressed ( untranslated
regions are called introns.
DNA Methylation
Nucleotides can be modified by addition of methyl groups.
Methylation helps to recruit some proteins that repress gene expression (condenses the chromatin –
tighter coil)
Histone Methylation: may ether increase or decrease gene expression depending on the level of
methylation
Acetylation: Decondenses chromatin and opens it. Acetylation decreases overall positive charges of
histones allowing DNA to loosely coil, facilitating gene expression
Progeria: Progeria: Progeroid syndrome –Causes patients to age faster. Histones get methylated
abnormally – inhibiting chromatin organization this leads to mutation on lamin which leads
mutated lamin protein (component of nuclear envelope ) & disrupts nuclear structure , Cell
division effected .
Chromosomes: Within nucleus we have
23pairs of chromosomes 22 pairs
(homologous chromosomes) plus X Y or XX
One pair of homologous chromosomes is
inherited form mother and one from father
.Together, a full set of chromosomes
represents an organism’s genome. Ends of
chromosomes are called telomeres has about
2500 repetitive of TTAGGG

To divide, cells must first replicate their entire

genome, during cell division, chromosomes supercoil
into highly condensed structural forms known as
metaphase chromosomes. Before cellular division
occurs, each chromosome consists of two identical
Telomeres DNA molecules, referred to as sister chromatids joined
at the centromere( by proteins called cohesins.

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