Unit II - Principles of Inheritance
DNA and DNA replication
February 9, 2000
Readings: Starr text: Ch 12, front page, 12.1 - 12.6
CD-ROM: great animations of DNA!
Outline: Exam 1 results |
I. DNA - Structure of the Macromolecule (continued from Ch 3)
DNA is a nucleic acid - a polymer - that contains multiple copies of 4 nucleotide monomers - A, C, G, and T (Fig 12.6) arranges in a spiral staircase shape
The backbone, or "stair rails" consists of repeating nucleotides joined sugar-to-phosphate - a sugar-phosphate backbone
The nucleotides, when joined together, polymerize to form a long strand, the backbone of which is repeating sugar and phosphate groups that twist around each other to form a double helix "staircase". (Fig 12.7)
The nitrogenous bases, "rungs", are held together by hydrogen bonds between the A and T and the C and G nucleotides:
II. The Discovery of DNA as the Genetic Material
In the early 1900s it was discovered that chromosomes controlled heredity
- But - it was also known that chromosomes consisted of 2 compounds DNA and protein.
- So which one molecule was responsible for heredity?
Most scientists thought proteins were the hereditary material - their R groups are diverse and have numerous interesting chemical properties
Nucleic acids like DNA seemed too "uniform" to be able to account for the thousands of traits of an organism - no one could imagine how DNA could carry genetic information - chemically it seemed like a rather "boring" molecule
However, several key experiments provided evidence that DNA is the genetic material:
1. Griffith (1928), Avery, Oswald, and MacLeod (1944): determined that DNA (not protein) could transform a bacteria R strain to a deadly S strain (Fig 12.3)
- 2. Chargaff (1947): detemined that the ratio of nucleotides was always the same in a given organism: Chargaff's rule: A = T and C = G (Section 12.2)
- 3. Hershey and Chase (1952): determined that viral DNA, not protein shell, enters cell upon infection to produce more virus particles. Hershey receives Nobel Prize, 1969. (Fig 12.4)
Finally, there was acceptance that DNA was in fact, the genetic material. The race was on to solve the puzzle - how could DNA trsnamit genetic information? What was the 3-dimentional structure of DNA?
The race: between Linus Pauling, Rosalind Franklin and Maurice Wilkins, and James Watson and Francis Crick
Watson and Crick
(1953): Built a model based on what was known about the structure of DNA
from X-ray crystallography (done by Rosalind Franklin and Maurice Wilkins)
and the experiments mentioned above.
Watson and Crick submitted a one-page paper to the journal Nature. They ended the paper with this subtle statement:
"It has not escaped our notice that the specific pairing that we have postulated immediately suggests a possible copying mechanism for the genetic material".
Shortly after that (1962) they bought their tickets to Stockholm!! Maurice Wilkins was also given the Nobel Prize (please read essay about Rosalind Franklin 12.3).
III. DNA its role in the cell
Any hereditary material has to have at least three functions. It must:
- 1. Replicate - make copies of itself - that may be passed down from cell to cell and from generation to generation (Today's lecture)
- 2. Control the activities of the cell - DNA encodes directions to make proteins that control cellular growth and metabolism. (Next week!)
- 3. Undergo mutations - permanent genetic changes that are passed on to offspring. (Genetics - coming soon!)
IV. DNA replication - remarkable in its speed and accuracy
Every time one of our cells divides, our DNA first has to be replicated - copied. In fact, 3 billion base pairs have to be copied precisely in 4-6 hours!!!! How does this event occur??
The DNA double helix is perfectly suited for replication because each strand can serve as a template (mold) to produce a shape opposite to itself.
A cast of enzymes and proteins accomplish DNA replication: (Fig 12.4)
1. The two strands of DNA are "unzipped" (H-bonds broken between bases) by the enzyme DNA helicase
2. New nucleotides are inserted by complementary base pairing (A to T, C to G etc) by the enzyme DNA polymerase
3. New nucleotides are linked together at their sugar-phosphate groups by the enzyme DNA ligase, forming a new double helix from one strand of "old" and one strand of "new" DNA. Because the DNA molecule contains one new strand and one old strand, the replication process is termed semi-conservative.
4. DNA repair enzymes "proofread" and correct mistakes
5. DNA is organized on a protein "scaffold": Each chromosome is one giant molecule of DNA millions of base pairs long. If stretched out, this would equal ~1 inch of DNA per chromosome! Histone proteins bind tightly to DNA and keep the chromosomes wound up tightly around "spools" of histones called nucleosomes.
6. After DNA replication, 2 complete DNA molecules are present, identical to each other and to the original DNA molecule
Learning Objectives: 1. Summarize experiments performed by the following scientists, which provided evidence that DNA is the genetic material:
2. Describe the structure of DNA with regard to the sugar phosphate backbone and the nucleotide bases. What is the 'base-pairing' rule (Chargaff's rule)? 3. Explain the three important features of DNA as the molecule of heredity 4. Explain the roles of DNA polymerase, DNA ligase, and DNA helicase, and DNA repair enzymes in DNA replication. What the end result of DNA replication? |
"Pssst...Bob, you're unzipped!"
"Double Helix for the home..."
