DNA Structure


Discovery history

Your online textbook provides a very thorough history of DNA.  I find this stuff interesting, but you may not be so fascinated by it.  Although all discoveries are important, there are a few to point out.  The very beginning of DNA discovery starts in the 1860s when Miescher discovered nucleic acids.  Called them nuclein because he isolated them from the nucleus.  Various experiments using bacteria further clarified knowledge about DNA.  We will use Chargaff’s rules for base pairing based on his findings that the number of adenine nitrogenous bases always equaled the number of thymine nitrogenous bases and the same pairing occurred for guanine and cytosine.  My favorite story of DNA discovery is the final push to discovery of the shape of DNA in the 1950s.  These men here, Watson and Crick, played around with physical models of the components of DNA until the came up with the double helix structure.  This x ray picture here on the right, taken by Rosalind Franklin, helped their conclusions by providing a top down picture of the double helix.  Think of looking down a spiral staircase from the top.  Strangely, Rosalind Franklin died of cancer.  She shoulda worn her lead apron.


Nucleic Acids

Many terms that refer to DNA that get confusing for students. Back in chapter 3 we loosely defined the term nucleic acids to include 2 type of nucleic acids one with a deoxyribose sugar called DNA and the other with a ribose sugar called RNA.  I have taught from other books that consider the molecule ATP to be a nucleic acid because it loosely meets the definition.  To be classified as a nucleic acid a molecule has to consist of building blocks called nucleotides which are pictured here as little lego pieces. RNA has only one stack of lego pieces whereas DNA has 2 stacks of lego pieces bonded together by little black dots.  Kidding.  DNA has 2 strands of nucleotides that are bonded together by hydrogen bonds.


Nucleotides

The nucleotides, of legos from the previous slide, also have their own three components: a phosphate group, very common in your body, a sugar, also common, and a nitrogenous base, common in everything you eat.  It’s these nitrogenous bases that you may be familiar with and correlate to that AGGTCA sequence of letters you might associate with DNA.  Like the movie GATTACA.  There are 5 nitrogenous bases that are divided into 2 major groups called pyrimidines and purines. These groups separate the nitrogenous bases by shape.  These shapes allow the purines and pyrmidines to bond together with those hydrogen bonds that bind the DNA strands together.  The shapes of these molecules are so specific that the purine gladdening will only form hydrogen bond with the pyrimidines cytosine. Adenine will bond with both thymine and uracil.   However, and this  is very important to note that sign mean is only found in a DNA molecule where is uracil is only found in an RNA molecule. There are questions on the quiz that students will answer with something about uracil, and then I’ll take points off and say: this question


Double helix

Let’s go back to our analogy with the legos for a moment. We have one molecule of DNA with 2 strands of nucleotides that are bonded together by hydrogen bond. You can see this on the picture on the far left of this slide. Let’s extend that analogy and think of a ladder.  The rails of the ladder or the place where you would put your hands on the ladder are composed of the sugars and the phosphates that are in each of the individual nucleotides. The rungs of the ladder or where you would put your feet are made up of bonded nitrogenous bases of the nucleotides.  Because of the specific nature of the bonding of the strands this structure does not stay as a ladder but starts to twist itself into a structure that is known as a double Helix.  The picture on the right shows you with commonly called the ribbon model of DNA.  Note how the rails of the ladder are blue and yellow showing you the alternating sugar phosphate backbone. And note how the rungs of the ladder are the they nitrogenous base is paired with hydrogen bond. Why the hydrogen bonds?  They are weak.  This makes the DNA easy to break apart and reform in order to duplicate it or make proteins from it.


Ends

When we consider DNA for some of the lab exercises, students get tripped up by this concept.  When DNA orients itself into the double helix, there ends of each strand of DNA has a different chemical composition.  The top end of the left strand has a phosphate group on it, and so we call this the 5 prime end.  Check out that the bottom end of the right strand has the same 5 prime end.  The bottom end of the left strand has an OH on it and this is called the 3 prime end.  Again, note the top right 3 prime end.  So, the DNA strands have a mirror image in this respect of 5 and 3 prime ends.  What we are going to find out is that proteins that replicate the DNA or “read” the DNA to make proteins will move from 5 to 3 prime. 


Dna packaging in eukaryotes

In this picture here, we have a chromosome on the left which is a condensed structure of DNA.  When DNA is condensed into a chromosome like this the sequence on the DNA is really not accessible for replication or for making proteins.  It’s too tightly packed.  I once had a video that said that a molecule of DNA can be as long a 9 meters.  How, then can 46 of them fit inside the nucleus of one cell?  Your DNA exists in your nuclei as these condensed, space saving structures.  To make these structures, the DNA winds around proteins called histones to make a combined structure called a nucleosome.  This is like rolling instead of folding your cloths to get them in a suitcase; rolling condenses them more than folding…supposedly.  You can see a histone and its four parts here in the inset on the right.  Note how the DNA double helix is wrapping around these histones.  Histones complicated things in the beginning of DNA discovery.  Histones and DNA were isolated from nuclei and the question was: which one of these things was being passed down?


Dna packaging in Prokaryotes

DNA packaging in prokaryotic cells, Bacteria and Archaea, is very different.  These single-celled organisms have only one big chromosome, and it is not bound in a nucleus. It is usually condensed, or packed into a region called the nucleoid.  But, remember, there is no membrane around the nucleoid.  An exzyme names gyrase helps keeps the bacterial chromosome coiled into a structure some genius named a supercoil.  Seriously, someone in a room somewhere was like: I got it!  Supercoil!  And some other person told them that they were a genius.  I know you’re thinking that these single celled animals meet all the requirements of like, just like you do, but they do that with only one chromosomes whereas humans require 46 chromosomes.  Bacteria also have little circular pieces of DNA called plasmids.  These plasmids can carry genes on them and also can be exchanged not only between bacteria of the same species but they can be exchanged between bacteria of different species.  This is significantly different then the limitations that eukaryotic species have in terms of exchanging DNA. Although I guess coronavirus may have changed that a little bit in the recent past.


Telomeres

Another major difference between prokaryotic and eukaryotic chromosomes is the presence of a telomere which is a short sequence of DNA on either end of a chromosome.  You can see the telomeres on this duplicated chromosome here as the darkened ends of each sister chromatid.  Every time your cells go through mitosis they lose just a little bit of this DNA sequence that makes up the telomere.  This is quite important because once the telomere is gone, you will starting losing DNA that might carry instructions for an important gene.  What we see with experimentation on telomeres is that the cell stops replicating all together once the telomere “cap” is eroded away..  This is what happens in all of your somatic cells. Every time they go through mitosis they lose a little bit of DNA. It was discovered that adult stem cells have an enzyme named telomerase that is capable of maintaining these telomeres in the chromosomes in your stem cells.  Only your stem cells. 


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