THE STRUCTURE OF DNA

The Structure of DNA

SCIENCE LEAPS FORWARD:

    In 1665 Robert Hooke first described a cell. 1861 Louis Pastuer proved that microbes are responsible for illness. In 1883 Chromosomes were discovered. In 1902 the application of Medelian inheritance to human inheritance of a genetic disease leap our understanding of inherited diseases forward.  1928 saw the discovery of penicillin by Alexander Flemming. In 1950 Linus Pauling discovered the structure of amino acids.  In 1953 Watson and Crick discovered the structure of DNA.  Frederick Sanger discovered how to sequence DNA in 1977. Since that time, new discoveries of medicine, cell structure and function, genes, gene therapies, and immunizations have come almost annually. The space race created many new innovations, and those innovations were later enjoyed by the public. Examples of this are artificial limbs, scratch resistant lenses, the insulin pump, Lasik surgery equipment, and solar cells.  Diseases and disasters have leap our understanding forward.  The HIV virus in the 1980's lead to research on viruses that helped us understand how they operate, and lead to anti viral medicines.  The RNA vaccine was studied, for perhaps use against cancer, by  the company ModeRNA.  It had gone through Monkey trials, which is the step before human testing, but by 2019 the company had lost over 1 billion dollars and was ready to close its doors......then Covid 19 happened and the US Government chose to loosen FDA testing restrictions.  The company was able to build a vaccine in one week.  It took a few months longer to get it accepted for emergency use against Covid-19 virus.   We would not be where we are today without the curiosity and work of hundreds of scientists, and the hardship and suffering of crisis.  Some who thought they failed.  OUT OF ALL OF THESE LEAPS FORWARD, THE DISCOVERY OF THE STRUCTURE OF DNA AND HOW IT IS SEQUENCED HAS HAD THE GREATEST IMPACT ON MEDICINE AND THE STUDY OF BIOLOGY.  

THE DISCOVERY OF DNA's STRUCTURE

In 1951 Linus Pauling was able to determine the structure of amino acids in a protein called collagen.  Inspired by Pauling, two graduate students James Watson at Indiana University and Francis Crick of Cambridge University worked together to create a model of DNA.  By 1953 they were able to build that model.  The simplicity of the structure helped them solve an important riddle for scientists.  How can life be so similar at the molecular level and so diverse at the level of organisms.

Their success was built on the research of several scientists. 

Fred Griffith, an Army Medical officer was trying to make a pnuemonia vaccine discovered that bacteria could transfer their "how to cause infection" instructions to other bacteria, even after the infectious type bacteria was dead...so their instruction molecule must have survived.

Bacteriophage Experiments:

   Alfred Hershey and Martha chase used bacteriophages, which are viruses that attack bacteria, to discover if it was DNA molecule in the viruses or the proteins in viruses that transfer hereditary information.

Viruses replicate by attaching to a cell, then injecting genetic material into a cell, and then the cell does the work of replicating the virus and the cell dies in the end. The protein part, the shell, of a virus stays outside the cell.  The DNA portion of a virus is injected into the cell. 

Hershey and Chase knew that the protein molecules  for bacteriophage viruses had the element sulfur in their protein shell molecules, but not phosphorus.  They knew that Bacteriophage DNA had phosphorus, but not have sulfur in it. 

So they grew bacteria in a sulfur medium, radioisotope ³⁵S.  Then they infected that bacteria with bacteriophage viruses. The viruses protein shells that replicated in those bacteria were now "tagged" with ³⁵S. They then whirred the bacteria and viral bodies, and those viral bodies on the outside of cells fall off and are separated from the bacteria cells.  All the tagged protein was in the viral bodies not inside the cells.

Then they did the same experiment, but with  a radioisotope of Phosphorus, which is part of the DNA molecule, ³²P. In this case, when they whirred the bacteria and bacteriophages, the DNA material, tagged with 32P, stayed inside the bacteria cells.  They then knew that it was the DNA that was the instructions to cells to duplicate the virus...in other words DNA was the molecule of inheritance.  

Rosalind Franklin Diffraction Experiments:

Franklin developed an X-ray diffraction technique to look at the structure of the DNA molecule.  She spun, and spooled each DNA molecule into a long gossamer fiber like cotton candy.  Then she bombarded the fiber with x-rays.  The long DNA molecule scattered the x-rays, like light is scattered by rain into a rainbow.  From this she was able to mathematically determine that the sugar and phosphate portions of DNA were on the outside of the molecule and the bases were positioned inside of the molecule. 

DNA STRUCTURE:

DNA consists of two strands held together at their bases by hydrogen bonds.

Hydrogen Bond-a weak attraction between molecules, due to their slight polar charges.

These bonds only form in DNA when the two strands run in opposite directions and twist together in a "double helix", like a circular stairway. Proteins called scaffolds also help keep loops untangled, by holding up unused portions of DNA, the introns. 

Proteins called histones wind up the DNA molecule like thread on a spool and keep it from becoming tangled. 

Four different nucleotide molecules make up DNA.  A nucleotide is a monomer- the building block of one of the types of organic molecules. Each Nucleotide has a five carbon sugar and that sugar is attached to a phosphate group.  Opposite of the phosphate group, a base is attached to the five carbon sugar.  There are only four bases.

Adenine= A

Guanine=B

Thymine=T

Cytosine=C

Purines and Pyrimidines are nitrogenous bases that make up the two different kinds of nucleotide bases in DNA and RNA. The two-carbon nitrogen ring bases (adenine and guanine) are purines, while the one-carbon nitrogen ring bases (thymine and cytosine) are pyrimidines.

ONLY TWO KINDS OF BASE PAIRINGS OCCURE ALONG THE ENTIRE LENGTH OF THE MOLECULE:

A-T 

G-C

However the order and amount of base pairing are very different between species.  Base parings are a constant for ALL SPECIES.  Base sequence is different for all species.  

THE REPLICATION OF DNA

The hereditary information in a cell is duplicated prior to cell division.  Hydrogen bonds hold together the two nucleotide strands.  Helicase, an enzyme, easily breaks these bonds and the two strands start to detach and unwind from each other.  The cells nucleolus has a stock pile of free nucleotides, Adenine, Guanine, Cytosine, and Thymine.  DNA Polymerase, another enzyme, attaches the nucleotides to the exposed bases on the parent strand of DNA.  Each  parent strand remains in tact while a companion strand is assembled on it.   One strand is called the leading strand and one strand is called the lagging strand. Remember the strands run in opposite directions.  The leading strand is easily assembled continuously. The lagging strand is assembled in fragments called Okazaki Fragments, and then later continuously bonded by more enzymes. The parent and companion strand twist into a double helix.  So each new DNA molecule is really half old and half new.  

DNA REPAIR

Two enzymes, DNA Polymerase and DNA Ligase, are part of a team of enzymes that help repair DNA. If bases in one srand become altered, DNA polymerase "reads" the complimentary sequence on the other strand, then restores the original sequence.  Ultraviolet radiation from the Sun, tanning beds and lamps, are causes of molecular damage to DNA, as are free radicals of Oxygen, which are biproducts of cellular respiration.  These can nock out or damage the bases, or they can made them covalently bond together, in a bulky molecule called a thymine dimer.  Normally our DNA repair team gets rid of dimers, but if the repair team of enzymes is also damaged or can't keep up, the dimers accumulate and become a cancer.  An example of this cancer is basil cell carcinoma, which must be cut away from the skin, leaving disfigurement.  Mohs surgery is an advancement in removal of basil cell carcinoma.  It is a microsurgery where tiny bits of the tumor is removed and examined by a lab to find the edges of the tumor while the patient waits.  It is closed with plastic surgery techniques, and leaves very little scarring.