We have already examined two of the three major parts of the cell: the plasma membrane (including its transport properties) and the cytoplasm (including its organelles). Now we turn to the third major part of the cell, the nucleus.

The nucleus is bounded by a double membrane (two layers of phospholipid bilayer) and contains the materials needed to control all parts of the cell. The genetic material — deoxyribonucleic acid (DNA) and three forms of ribonucleic acid (RNA) — are made in the nucleus.

Because structure is related to function, we must understand the structure of the DNA molecule in order to understand the function of DNA as the genetic material. The story of the discovery of the structure of DNA tells us a lot about how science is done. In the Canvas course, you will find articles describing the history of this key discovery, but here’s the shortened version, which is helpful for understanding DNA structure and function.

Organic chemists found special, unusual molecules in the nucleus and by the end of the 19th century, these were called “nucleic acids” — because they were isolated in large quantities from the nucleus and because they had negative charges, that is, they had donated an H⁺ (Unit 2).

You will do this type of nucleic acid isolation for yourself, using strawberries as the source material, in the laboratory portion of the course.

Before World War II, scientists did experiments which showed that the inheritance of a cell’s characteristics was encoded in the deoxyribonucleic acid (DNA). Scientists of all types were engaged in the war effort during the first half of the 1940s, but after the war, there was a large pool of funding available for studies. There was also a large pool of biologists, chemists, and physicists who had tired finding new ways to kill people and were eager to work on problems related to the origin of life, including the structure of DNA.

The race was on. Two groups took an early lead: Linus Pauling’s American team at the California Institute of Technology chemistry lab; and an English team consisting of Francis Crick at Cambridge and Maurice Wilkins at King’s College. (You may remember Pauling from his description of electronegativity in Unit 2.)

Pauling proposed a triple helical structure for DNA. He had already discovered that collagen, the main protein of connective tissue, had a triple helical structure so his lab had experience with this type of molecule. Francis Crick at Cambridge, joined by a brash young American named James Watson, was toying with the idea of a double helical structure for DNA. Both groups were desperate for data to support the models they were building (literally — you can see one of those cardboard models built by Watson on the left and Crick on the right).

Meanwhile, at King’s College, London, Maurice Wilkins had hired the pre-eminent X ray crystallographer of her generation, Rosalind Franklin. There were only a few dozen X ray crystallographers in the world at that point, but everyone agreed she was the best.

She was able to obtain beautiful images of crystallized (i.e. pure) DNA. The best of those was shown on page 6-2; it’s so famous it is known to scientists as “Image 51”. To you and me, this doesn’t look like much more than a pair of dotted lines forming an X but Franklin immediately saw that it described a double helix (right diagram). Still, being a very meticulous scientist, she felt the need to collect more data before presenting her work publicly.

On a visit to Wilkins’ lab, Watson and Crick saw Image 51 and immediately recognized how critical it was for their modeling. They arranged to obtain it without Franklin’s permission (but with the assent of Wilkins, who, as lab director, had ownership of the data).

They immediately finished their modeling work based on Franklin’s data and announced their finding on February 28, 1953. They published their paper in Nature on April 25 of the same year; that paper is reproduced in Objective 5. It will be important for our understanding of the DNA copying mechanism.

The important features of the DNA molecule have been understood ever since and are summarized in the next image.

1. The DNA molecule is a double helix, with two backbones of deoxyribose sugar and phosphate connected with a specific direction. The first phosphate is attached to the 5’ carbon of the deoxyribose molecule, and the next phosphate is attached to the 3’ carbon of the same deoxyribose. This is called the 5’ to 3’ direction.
2. The backbones of the two strands of the double helix are antiparallel to each other. Notice that in our drawings, one runs up the page in the 5’ to 3’ direction while the other runs down the page in the 5’ to 3’ direction.
3. There are four complex organic molecules that are rich in nitrogen and whose amino groups contain positive charges and are, therefore, called nitrogenous bases. Two are classified as purines and two are pyrimidines. These form base pairs because of their hydrogen bonding properties. The purine adenine (A) always pairs with the pyrimidine thymine (T). The pyrimidine cytosine (C) always pairs with the purine guanine (G). The mnemonic for these base pairing properties is “apple trees and chewing gum” which represents the first letters of each base pair.

The structure of ribonucleic acid (RNA) is similar but different in a few key aspects. RNA tends not to form double-stranded structures but it does have some limited double-stranded regions, for example in a type of RNA called transfer RNA. RNA is mostly single-stranded. RNA does not use the base thymine, but instead uses a base called uracil (U). Thymine and uracil are isomers. The only difference between thymine and uracil is that thymine has a methyl (–CH3) group which does not change their base pairing properties; their hydrogen bonds attach them to adenine and nothing else.

The single-stranded nature of the RNA molecule results in several major differences in how cells manage DNA and RNA, which will be the thread of the story told in this Unit.

Returning to our examination of DNA structure, we now confront a major problem for cells. Each cell of the human body contains about 3 m of DNA double helices, but that 3 m has to be packed into a nucleus for almost every one of the 10 trillion cells making up the human body.

Packaging of DNA 

DNA exists in two forms: an unspooled euchromatin and a tightly-packed heterochromatin.

Euchromatin, as we will see, is DNA that is in use (i.e. being transcribed, or ready to be transcribed on a moment’s notice, Objective 3) while heterochromatin is how DNA is packaged for cell division (Objective 6).

We have to pack 3 meters of DNA into each of your 10 trillion human cells. However, DNA is an acid, and as we learned in Units 2 and 3, acids have negative charges. All those negative charges will repel each other and make packing impossible.

In order to neutralize the negative charges, we need proteins with a large number of positively-charged (i.e. basic) –R groups: lysine, arginine, and histidine. These proteins are called histones and they’re rich in those three amino acids so they have plentiful positive charges.

First, the DNA strand is wound around the histones.

Then, the histone-DNA complex, with no excess charges, is packed into ball-like structures called nucleosomes. These are described as a “beads on a string” arrangement, with nucleosomes representing the beads and DNA the string.

DNA wound around histones and formed into nucleosomes can now be assembled into a structure visible under the light microscope called chromatin because of its intense color when stained with microscope dyes. The chromatin is packed into chromatids.

Amazingly, each chromatid is one single, continuous DNA molecule with associated proteins. For example, human chromosome 1 consists of two chromatids; each chromatid is 247,000,000 (2.47 x 10⁸) base pairs (165,000,000,000 or 1.65 x 10¹¹ Daltons molecular weight). This is 1/13 of the DNA in the human cell, which collectively is 3,300,000,000 (3.3 x 10⁹) base pairs with a molecular weight of 2,200,000,000,000 (2.2 x 10¹²) Daltons.

Finally, two chromatids, each with almost identical but slightly different DNA (Objective 8), are joined together into an X- or Y-shaped structure called a chromosome.

Along with the chromatin, which stains intensely with dyes used by light microscopists, there is a fuzzy round ball of densely-staining material inside the nucleus. This fuzzy ball is called a nucleolus.

The nucleolus is the machine shop where we create RNA, including the RNA component of the macromolecular machine called the ribosome. The ribosome is a protein-making machine. We met ribosomes briefly in Unit 5, and will look at them in depth below.

DNA is the most stable of molecules, almost as solid as a rock (literally). DNA, degraded but still recognizable, has been found from organisms that existed 2 million years ago.6-10

RNA, on the other hand, is made to be unstable.

In particular, messenger RNA, which we’ll see is used to make proteins, does not hang around long. A moment’s reflection will (hopefully) make it clear why. Think about what has to stay constant, and what has to change, as your body responds to whatever life throws at you over a 100-year lifespan.

These three types of RNA are made by different RNA polymerases. As the name tells us, RNA polymerase is an enzyme (ending in –ase) that forms an RNA polymer from individual ribonucleotides.

We will see how messenger RNA (mRNA) is made from a DNA template inside the nucleus. Messenger RNA is very unstable. Most messages are destroyed immediately after they are used; this allows the cell to change its protein composition dynamically by changing how much message is made. This is called transcriptional control.

The ribosomal RNA (rRNA) components of the ribosome are (mostly) made within the nucleolus. These raw materials are shipped out the nuclear pores. In the cytoplasm, rRNA and proteins are assembled into the ribosome. Ribosomes either exist as free ribosomes or as part of the rough endoplasmic reticulum (RER). Either way, they operate as factories that translate the RNA language of nucleic acids into the amino acid language of proteins.

The third type of RNA we’ll consider is transfer RNA (tRNA), another relatively stable type of RNA that participates in protein synthesis. If ribosomes are the protein factories, then recall that tRNAs are the fleet of trucks that bring raw materials to the factory. Recall also that proteins are made up of amino acids, so the raw materials of protein synthesis are amino acids. tRNA has an unusual cloverleaf shape in schematic pictures. tRNA also has some oddball and modified ribonucleotides that we won’t discuss.

mRNA and tRNA differ from one another in shape and size. The mRNA molecule is simply a long, single strand polymer of linked ribonucleotides. The tRNA is also a long, single strand, but folds to create double-stranded sections which give it a characteristic “cloverleaf” shape with an acceptor arm for binding a single amino acid. In drawing rRNA (not shown), its difficult to separate the rRNA from the rest of the ribosome. Just remember that the two ribosomal subunits (small and large) are each comprised of rRNA and ribosomal proteins.