Concept 15 DNA and proteins are key molecules of the cell nucleus.

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Phoebus Levene's work in determining nucleic acid structures was analytical and rigorous while his tetranucleotide hypothesis was almost completely based on theoretical data. Levene "overlooked" data that disputed his hypothesis.

Hmmm...

In the 1920's and 1930's, many scientists accepted Levene's tetranucleotide theory. Could scientific history be changed if Levene didn't propose such a theory?

Hello, I'm Friedrich Miescher. I was interested in the chemistry of cells. In 1869, I began working with white blood cells. White blood cells are the major component of pus from infections. I collected a lot of pus from bandages at the local hospital. I used a salt solution to wash the pus off the bandages. When I added a weak alkaline solution to the cells, the cells lysed and nuclei precipitated out of the solution. From the cell nuclei I isolated a unique chemical substance, which I called nuclein. I found nuclein in every cell type I tested. Chemically, nuclein is high in phosphorus. Therefore, I thought nuclein mainly functioned as the cellular storehouse for the phosphorus atom. In my lifetime, we were not able to show any other clear biological function for nuclein. I'm Phoebus Levene. By the early 1900's, we knew that Miescher's nuclein was a mix of proteins and nucleic acids. There are two kinds of nucleic acids. I'm Phoebus Levene. By the early 1900s, we knew that Miescher's nuclein was a mix of proteins and nucleic acids. There are two kinds of nucleic acids. DNA �€” deoxyribonucleic acid �€” is found mainly in the nucleus. RNA �€” ribonucleic acid �€” is found mainly in the cytoplasm. Although most of my work was on the chemical nature of DNA, let's first talk about proteins. Proteins are made up of 20 different subunits �€” amino acids. These amino acids are chemically linked together to form protein chains. With 20 different amino acids to build from, even a small protein can have millions of sequence combinations. Let's take an example where we link just four amino acids. Since any one of 20 amino acids can occur at each position, there are 160,000 different possible combinations. Therefore, proteins come in many different shapes and sizes. I believed that this variety made proteins a good candidate as the molecules of heredity. DNA, the molecule that I worked on, has only four different units, called nucleotides. A nucleotide is made up of three elements: A nucleotide is made up of three elements: phosphate... A nucleotide is made up of three elements: phosphate, deoxyribose sugar... A nucleotide is made up of three elements: phosphate, deoxyribose sugar, and a nitrogenous base. The carbons of the deoxyribose sugar are numbered 1-5. In a nucleotide, the nitrogenous base is always bound to carbon#1, a hydroxyl group (OH) is bound to carbon#3 and the phosphate group is bound to carbon#5. Each of the four nucleotides has its own distinctive nitrogenous base. Each of the four nucleotides has its own distinctive nitrogenous base. I figured out that nucleotides are linked by a phosphodiester bond: one phosphate group binds to two sugars through the hydroxyl group on carbon#3 of one sugar and carbon#5 of another sugar. The phosphodiester bonds give the linkage between nucleotides a directionality: from carbon#5 to carbon#3, 5 prime (5') to 3 prime (3'). I thought that nucleotides were found in equal amounts in DNA molecules. So, I proposed that DNA must be a tetranucleotide �€” a linked series of four where the order was always the same. In 1938, I found that DNA is a much larger molecule than anyone had thought. It made more sense to think of DNA as a polymer, a long-chain molecule made up of repeating units of tetranucleotides. It was hard to see how DNA could be "intelligent" enough to carry hereditary information. In my model, DNA is made up of tetranucleotide blocks; whereas proteins have an alphabet of 20 amino acids. In my opinion, proteins were a better choice as the nuclear hereditary material. C#4 C#5 Each of the four nucleotides has its own distinctive nitrogenous base. CYTOSINE Each of the four nucleotides has its own distinctive nitrogenous base. ADENINE O CH 2 H HO P OH H C 3 THYMINE 2 GUANINE I figured out that nucleotides are linked by a phosphodiester bond: one phosphate group binds to two sugars through the hydroxyl group on carbon#3 of one sugar and carbon#5 of another sugar. PHOSPHODIESTER BOND The phosphodiester bonds give the linkage between nucleotides a directionality: from carbon#5 to carbon#3, 5 prime (5') to 3 prime (3'). I thought that nucleotides were found in equal amounts in DNA molecules. So, I proposed that DNA must be a tetranucleotide �€” a linked series of four where the order was always the same. TETRANUCLEOTIDE In 1938, I found that DNA is a much larger molecule than anyone had thought. It made more sense to think of DNA as a polymer, a long-chain molecule made up of repeating units of tetranucleotides. DNA CHAIN It was hard to see how DNA could be "intelligent" enough to carry hereditary information. In my model, DNA is made up of tetranucleotide blocks; whereas proteins have an alphabet of 20 amino acids. In my opinion, proteins were a better choice as the nuclear hereditary material. /dnaftb/concept_15/con15anigene.html