Ayaz Latif Siyal

M.Sc Plant Breeding & Genetics

latifayazsiyal@gmail.com
+923337579719
P/O Pacca Chang, Taluka Faiz gunj, District Khairpur Mirs Sindh Pakistan.

DNA
DNA Double Helical Structure, History, Gene & Molecular Level.

DNA, abbreviation of deoxyribonucleic acid, organic chemical of complex molecular

structure that is found in all prokaryotic and eukaryotic cells and in many viruses. DNA codes
genetic information for the transmission of inherited traits.

Deoxyribonucleic acid or DNA is a molecule that contains the instructions an organism needs
to develop, live and reproduce. These instructions are found inside every cell, and are passed
down from parents to their children. All living things have DNA. And whether it comes from
you, a pea plant, or your pet rat, it's all the same molecule. It's the order of the letters in the
code that makes each organism different.
History
Friedrich Miescher and Richard Altmann
Friedrich Miescher (1844-1895) discovered a substance he called "nuclein" in 1869. Later he
isolated a pure sample of the material now known as DNA from the sperm of salmon, and in
1889 his pupil, Richard Altmann, named it "nucleic acid". This substance was found to exist
only in the chromosomes.

Frederick Griffith
Frederick Griffith, a scientist, was working on a project in 1928 that formed the basis that
DNA was the molecule of inheritance. Griffith's experiment involved mice and two types of
pneumonia one was virulent and the other non-virulent. He injected the virulent pneumonia
into a mouse and the mouse died. Next he injected the non-virulent pneumonia into a mouse
and the mouse survived.

After this, he heated up the virulent disease to kill it and then injected it into a mouse. This
time the animal survived as predicted. Last he injected non-virulent pneumonia and virulent
pneumonia that had been heated and killed, into a mouse. This time the mouse died.

Griffith speculated that the killed virulent bacteria had passed on a characteristic to the non-
virulent one to make it virulent. He believed this characteristic was in the inheritance
molecule. This passing on of the inheritance molecule was what he called transformation.

Oswald Avery
Oswald Avery continued with Griffiths experiment around a decade later to see what the
inheritance molecule was. In this experiment he destroyed the lipids, ribonucleic acids,
carbohydrates, and proteins of the virulent pneumonia. Transformation still occurred after
this. Next he destroyed the deoxyribonucleic acid. Transformation did not occur. He had
found the basis of the inheritance.

Phoebus Levene
In 1929 Phoebus Levene at the Rockefeller Institute identified the components that make up a
DNA Molecule. Those components are:

1. The four bases

a. Adenine (A)
b. Cytosine (C)
c. Guanine (G)
d. Thymine (T)
2. Sugar
3. Phosphate
He showed that the components of DNA were linked in the order phosphate-sugar-base. He
said that each of these units is a nucleotide and suggested the DNA molecule consisted of a
string of nucleotide units linked together through the phosphate groups. He suggested that
these form a 'backbone' of the molecule. However, Levene thought the chain was short and
that the bases repeated in the same fixed order. It was Torbjorn Caspersson and Einar
Hammersten who showed that DNA was a polymer.

Erwin Chargaff and Chargaffs rule

To understand the DNA molecule better, scientists were trying to make a model to
understand how it works and what it does. In the 1940s another scientist named Erwin
Chargaff found the pattern in the amounts of the four bases: adenine, guanine, cytosine, and
thymine. He took samples of DNA of different cells and found that the amount of adenine
was almost equal to the amount of thymine, and that the amount of guanine was almost equal
to the amount of cytosine. Thus you could say: A=T, and G=C. This discovery later became
Chargaffs Rule.

Rosalind Franklin and Maurice Wilkins

Thereafter two researchers Rosalind Franklin and Maurice Wilkins tried to make a crystal of
the DNA molecule. They wanted to take X ray pictures of the DNA to understand how DNA
works. These two scientists were successful and obtained an x-ray pattern. The pattern
appeared to contain rungs, like those on a ladder between to strands that are side by
side. They found that DNA had a helix shape.

Watson and Crick

In 1953, two scientists, James Watson and Francis Crick, were trying to put together a model
of DNA. They took a look at Franklin and Wilkin's picture of the X-ray and made their
model. They created a model that has not been changed much since then. Their model
showed a double helix with little rungs connecting the two strands. These rungs were the
bases of a nucleotide. They also found that if they paired Thymine with Adenine and Guanine
with Cytosine DNA would look uniform. This pairing was also in accordance with
Chargaff's rule.

DNA
DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other
organisms. Nearly every cell in a persons body has the same DNA. Most DNA is located in
the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be
found in the mitochondria (where it is called mitochondrial DNA or mtDNA).
The information in DNA is stored as a code made up of four chemical bases: adenine (A),
guanine (G), cytosine (C), and thymine (T). The order, or sequence, of these bases determines
the information available for building and maintaining an organism, similar to the way in
which letters of the alphabet appear in a certain order to form words and sentences.
DNA bases pair up with each other, A with T and C with G, to form units called base pairs.
Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base,
sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands
that form a spiral called a double helix. The structure of the double helix is somewhat like a
ladder, with the base pairs forming the ladders rungs and the sugar and phosphate molecules
forming the vertical sidepieces of the ladder.
An important property of DNA is that it can replicate, or make copies of itself. Each strand of
DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is
critical when cells divide because each new cell needs to have an exact copy of the DNA
present in the old cell.

Double Helix Structure of

DNA
Double helix is the description of the structure of a DNA
molecule. A DNA molecule consists of two strands that
wind around each other like a twisted ladder. Each strand
has a backbone made of alternating groups of sugar
(deoxyribose) and phosphate groups. Attached to each
sugar is one of four bases: adenine (A), cytosine (C),
guanine (G), or thymine (T). The two strands are held
together by bonds between the bases, adenine forming a
base pair with thymine, and cytosine forming a base pair
with guanine.

Gene
A gene is the basic physical and functional unit of heredity. Genes, which are made up of
DNA, act as instructions to make molecules called proteins.
Molecular Level

Introduction
DNA replication, or the copying of a cell's DNA, is no simple task! There are about 6.56.56,
point, 5 \text{billion}billionb, i, l, l, i, o, n base pairs of DNA in your genome, all of which
must be accurately copied when any one of your trillions of cells divides^11start superscript,
1, end superscript.The basic mechanisms of DNA replication are similar across organisms. In
this article, we'll focus on DNA replication as it takes place in the bacterium E. coli, but the
mechanisms of replication are similar in humans and other eukaryotes. Let's take a look at the
proteins and enzymes that carry out replication, seeing how they work together to ensure
accurate and complete replication of DNA.

The basic idea

DNA replication is semiconservative, meaning that each strand in the DNA double helix acts
as a template for the synthesis of a new, complementary strand. This process takes us from
one starting molecule to two "daughter" molecules, with each newly formed double helix
containing one new and one old strand.

DNA polymerase

One of the key molecules in DNA replication is the enzyme DNA polymerase. DNA
polymerases are responsible for synthesizing DNA: they add nucleotides one by one to the
growing DNA chain, incorporating only those that are complementary to the template.

Starting DNA replication

How do DNA polymerases and other replication factors know where to begin? Replication
always starts at specific locations on the DNA, which are called origins of replication and
are recognized by their sequence. E. coli, like most bacteria, has a single origin of replication
on its chromosome. The origin is about 245245245 base pairs long and has mostly A/T base
pairs (which are held together by fewer hydrogen bonds than G/C base pairs), making the
DNA strands easier to separate. Specialized proteins recognize the origin, bind to this site,
and open up the DNA. As the DNA opens, two Y-shaped structures called replication
forksare formed, together making up what's called a replication bubble. The replication
forks will move in opposite directions as replication proceeds.

Primers and primase

DNA polymerases can only add nucleotides to the 3' end of an existing DNA strand. (They
use the free -OH group found at the 3' end as a "hook," adding a nucleotide to this group in
the polymerization reaction.) How, then, does DNA polymerase add the first nucleotide at a
new replication fork?Alone, it can't! The problem is solved with the help of an enzyme
called primase. Primase makes an RNA primer, or short stretch of nucleic acid
complementary to the template, that provides a 3' end for DNA polymerase to work on. A
typical primer is about five to ten nucleotides long. The primer primes DNA synthesis, i.e.,
gets it started. Once the RNA primer is in place, DNA polymerase "extends" it, adding
nucleotides one by one to make a new DNA strand that's complementary to the template
strand.

Leading and lagging strands

In E. coli, the DNA polymerase that handles most of the synthesis is DNA polymerase III.
There are two molecules of DNA polymerase III at a replication fork, each of them hard at
work on one of the two new DNA strands. DNA polymerases can only make DNA in the 5' to
3' direction, and this poses a problem during replication. A DNA double helix is always anti-
parallel; in other words, one strand runs in the 5' to 3' direction, while the other runs in the 3'
to 5' direction. This makes it necessary for the two new strands, which are also antiparallel to
their templates, to be made in slightly different ways. One new strand, which runs 5' to 3'
towards the replication fork, is the easy one. This strand is made continuously, because the
DNA polymerase is moving in the same direction as the replication fork. This continuously
synthesized strand is called the leading strand. The other new strand, which runs 5' to 3'
away from the fork, is tricker. This strand is made in fragments because, as the fork moves
forward, the DNA polymerase (which is moving away from the fork) must come off and
reattach on the newly exposed DNA. This tricky strand, which is made in fragments, is called
the lagging strand.
The maintenance and cleanup crew

Some other proteins and enzymes, in addition the main ones above, are needed to keep DNA
replication running smoothly. One is a protein called the sliding clamp, which holds DNA
polymerase III molecules in place as they synthesize DNA.