8. DNA and RNA. The Molecular Basis of Heredity



DNA Repair Shops Inside Living Cells?

Discovery could help NASA cope with the health threat posed to astronauts by radiation.

Astronauts are regularly exposed to cosmic radiation and, on occasion, their DNA is damaged. Because DNA carries a cell’s genetic information, damage may result in cell death, cancers, or other abnormalities. Research has shown that cells have the ability to repair damaged DNA. However, while cells can often fix minor damage successfully, they sometimes botch major repairs that can make a cell even more prone to becoming cancerous. So rather than attempt to fix itself, the repair mechanisms can be blocked by enzymes, forcing a severely damaged cell to self-destruct. This actually keeps the astronaut healthier overall.

One hypothesis on how damaged DNA is repaired suggests that the repair happens right where the damage occurs. New research shows that some strands of DNA with minor damage are repaired on the spot. A second hypothesis proposes that cells move the most damaged DNA to special “repair shops” inside the cell. Scientists at NASA’s Space Radiation Program suggest that rather than trying to gather the repair enzymes at the damage site, it might be more efficient to keep all these enzymes in “shops” near the chromosomes and take damaged DNA to them.

Should exposure to radiation increase for Earth-bound organisms, it will be important for scientist to understand the molecular biology of DNA repair. This better understanding could enable medical professionals to limit or control radiation-induced illness.

• Why would self-destruction of a mutated cell be beneficial to the overall health of a multicellular organism?

• How can a single change in DNA result in a fatal abnormality?

• Would you support federal funding of research into DNA repair mechanisms if there was no increase in radiation reaching the Earth?


ü  Background Check

Concepts you should already know to get the most out of this chapter:

• The structure and chemical properties of proteins and nucleic acids (chapter 3)

• The organization of cells and their genetic information (chapter 4)

• The role of proteins in carrying out the cell’s chemical reactions (chapter 5)


8.1. DNA and the Importance of Proteins


This chapter focuses on what is notably life’s most important class of organic compounds, nucleic acids. Scientists around the world have performed countless experiments that revealed the significant roles played by these compounds. Deoxyribonucleic acid (DNA) has been called the “blueprint for life,” “master molecule,” and “transforming principle.”

Nucleic acids were discovered in 1869, when Swiss-born Johann Friedrich Meischer first isolated phosphate-containing acids from cells found in the bandages of wounded soldiers. In 1889 Richard Altman coined the term nucleic acid. However, it wasn’t until 1950 that DNA became the front-running candidate for the genetic material. It was the work of Americans Alfred Hershey and Martha Chase (1952) that directly linked DNA to genetically controlled characteristics of the bacterium Escherichia coli (How Science Works 8.1).

Today we know that all organisms use nucleic acids as their genetic material to:

1. store information that determines the characteristics of cells and organisms;

2. direct the synthesis of proteins essential to the operation of the cell or organism;

3. chemically change (mutate) genetic characteristics that are transmitted to future generations; and

4. replicate prior to reproduction by directing the manufacture of copies of itself.

The cell’s ability to make a particular protein comes from the genetic information stored in the cell’s DNA. DNA contains genes, which are specific messages about how to construct a protein. Most of an organism’s characteristics are the direct result of proteins. Proteins play a critical role in how cells successfully meet the challenges of being alive. For example, functional proteins like enzymes carry out important chemical reactions. Enzymes are so important to a cell that the cell will not live long if it cannot reliably create the proteins it needs for survival. Structural proteins like microtubules, intermediate filaments, and microfilaments are made with the help of enzymes. These proteins maintain cell shape and aid in movement.

Genetic information controls many cellular processes including:

1. the digestion and metabolism of nutrients, and the elimination of harmful wastes;

2. the repair and assembly of cell parts;

3. the reproduction of healthy offspring;

4. the ability to control when and how to react to changes in the environment; and

5. the coordination and regulation of all life’s essential functions.



Scientists Unraveling the Mystery of DNA

As recently as the 1940s, scientists did not understand the molecular basis of heredity. They understood genetics in terms of the odds that a given trait would be passed on to an individual in the next generation. This "probability" model of genetics left some questions unanswered:

• What is the nature of genetic information?

• How does the cell use genetic information?



Genetic Material Is Molecular

As is often the case in science, accidental discovery played a large role in answering questions about the nature and use of genetic information. In 1928, a medical doctor, Frederick Griffith, was studying two bacterial strains that caused pneumonia. One of the strains was extremely virulent (highly dangerous) and therefore killed mice very quickly. The other strain was not virulent. Griffith observed something unexpected when dead cells of the virulent strain were mixed with living cells of the nonvirulent strain: The nonvirulent strain took on the virulent characteristics of the dead strain. Genetic information had been transferred from the dead, virulent cells to the living, nonvirulent cells. This observation was the first significant step in understanding the molecular basis of genetics because it provided scientists with a situation wherein the scientific method could be applied to ask questions and take measurements about the molecular basis of genetics. Until this point, scientists had lacked a method to provide supporting data.

This spurred the scientific community for the next 14 years to search for the identity of the "genetic molecule." A common hypothesis was that the genetic molecule would be one of the macromolecules—carbohydrates, lipids, proteins, or nucleic acids. During that period, many advances were made in how researchers studied cells. Many of the top minds in the field had formulated the hypothesis that the genetic molecule was protein. They had very good support for this hypothesis, too. Their argument boiled down to two ideas. The first idea is that proteins are found everywhere in the cell. It follows that, if proteins were the genetic information, they would be found wherever that information was used. The second idea is that proteins are structurally and chemically complex. They are made up of 20 different amino acids that come in a wide variety of sizes and shapes to make proteins with different properties. This complexity might account for all the genetic variety observed in nature.

On the other hand, very few scientists seriously considered the notion that DNA was the heritable material. After all, it was found only in the nucleus and consisted of only four monomers (nucleotides). How could this molecule account for the genetic complexity of life?


Genetic Material Is DNA

In 1944, Oswald Avery and his colleagues provided the first evidence that DNA is the genetic molecule. They performed an experiment similar to Griffith's. Avery's innovation was to use purified samples of protein, DNA, lipids, and carbohydrates from the virulent bacterial strain to transfer the virulent characteristics to the nonvirulent bacterial strain. His data indicated that DNA contains genetic information. The scientific community was highly skeptical of these results for two reasons: (1) Scientists had expected the genetic molecule to be protein, so they hadn't expected this result. More importantly, (2) Avery didn't know how to explain how DNA functions as the genetic molecule. Because of the scientific community's mind-set, Avery's data were largely disregarded on the rationale that his samples were impure. Avery had already designed and carried out an experiment with appropriate controls to address this objection. He reported over 99% purity in the tested DNA samples. It took 8 additional years and a different type of experiment to establish DNA as the genetic molecule.

In 1952, Alfred Hershey and Martha Chase carried out the experiment that settled the question that DNA is the genetic material. Their experiment used a relatively simple genetic system—a bacteriophage. A bacteriophage is a type of virus that uses a bacterial cell as its host. The phage used in this experiment contained only DNA and protein. Hershey and Chase hypothesized that it was necessary for the phage's genetic information to enter the bacterial cell to create new phage. By radioactively labeling the DNA and the protein of the phage in different ways, Hershey and Chase were able to show that the DNA entered the bacterial cell, although very little protein did. They reasoned that since only DNA entered the cell, DNA must be the genetic information.


The Structure and Function of DNA

Researchers then turned toward the issue of determining how DNA works as the heritable material. Scientists expected that the genetic molecule would have to do a number of things, such as store information, use the genetic information throughout the cell, be able to mutate, and be able to replicate itself. Their hypothesis was that the answer was hidden in the structure of the DNA molecule itself.

The investigation of how DNA functioned as the cell's genetic information took a wide variety of strategies. Some scientists looked at DNA from different organisms. They found that, in nearly every organism, the guanine (G) and cytosine (C) nucleotides were present in equal amounts. The same held true for adenine (A) and thymine (T). Later, this provided the basis for establishing the nucleic acid base-pairing rules.

Rosalind Franklin used X-ray crystallography to determine DNA's width, its helical shape, and the repeating patterns that occur along the length of the DNA molecule. Finally, two young scientists, James Watson and Francis Crick, put it all together. They simply listened to and read the information that was being discussed in the scientific community. Their key role was in the assimilation of all the data. They recognized the importance of the X-ray crystallography data in conjunction with the organic structures of the nucleotides and the data that established the base-pairing rules. Together, they created a model for the structure of DNA that accounts for all the things that a genetic molecule must do. They published an article describing this model in 1952. Ten years later, they were awarded the Nobel Prize for their work.



1. What is a gene?

2. What four functions are performed by nucleic acids?