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Chapter 11: DNA and Its Role in Heredity
CHAPTER 11DNA and Its Role in Heredity
Chapter 11: DNA and Its Role in Heredity
The Structure of DNA
• In the 1950’s many researchers were trying to determine the structure of DNA.
• X-ray crystallography showed that the DNA molecule is a helix. (Franklin & Wilkins)
• Chargaff discovered that the amount of adenine equals the amount of thymine and the amount of guanine equals the amount of cytosine.
• What does this finding indicate?
Chapter 11: DNA and Its Role in Heredity
Figure 11.5
Figure 11.5
figure 11-05.jpg
Chapter 11: DNA and Its Role in Heredity
The Structure of DNA
• Watson and Crick proposed that DNA is a double-stranded helix with the two sides of DNA running in opposite directions (the strands are antiparallel),
• The two sides are held together by hydrogen bonds.
• What accounts for the uniform diameter of the double helix?
Chapter 11: DNA and Its Role in Heredity
Structure of DNA
• A purine (A or G) consists of a double ring molecule. A pyrimidine (C or T) consists of a single ring molecule. A purine always bonds with a pyrimidine thus maintaining a constant distance between the two sides of the DNA molecule.
• Review Figures 11.6 and 11.7
Chapter 11: DNA and Its Role in Heredity
Structure of DNA
What does it mean - the two DNA strands run in opposite directions?
Examine the phosphodiester bonds between nucleotides.
The 3’ carbon of one deoxyribose and the 5’ carbon of another deoxyribose are bonded.
One side of the DNA molecule has an unconnected 5’ phosphate group while the opposite end has an unconnected 3’ hydroxyl group.
Chapter 11: DNA and Its Role in Heredity
DNA Structure
Examine the other side of the DNA molecule. It just the opposite
Chapter 11: DNA and Its Role in Heredity
Figure 11.6
Figure 11.6
figure 11-06.jpg
Chapter 11: DNA and Its Role in Heredity
Figure 11.7 – Part 1
Figure 11.7 - Part 1
figure 11-07a.jpg
Chapter 11: DNA and Its Role in Heredity
Figure 11.7 – Part 2
Figure 11.7 – Part 2
figure 11-07b.jpg
Chapter 11: DNA and Its Role in Heredity
The Structure of DNA
Three features summarize the molecular architecture of DNA:
– The DNA molecule is a double-stranded helix.
– The diameter of the DNA molecule is uniform.
– The two strands run in different directions (they are antiparallel).
Chapter 11: DNA and Its Role in Heredity
Three Models for DNA Replication
• Conservative – original plus new strand• Dispersive – fragments of original DNA serve
as templates for two DNA molecules. • Semiconservative – parent strand serves as a
template for new strand • Review Figure 11.8
Chapter 11: DNA and Its Role in Heredity
The Structure of DNA
The sugar–phosphate backbones of each strand coil around the outside of the helix.
The nitrogenous bases point toward the center of the helix.
Hydrogen bonds between complementary bases hold the two strands together.
A always pairs with T (two hydrogen bonds). G always pairs with C (three hydrogen bonds).
Chapter 11: DNA and Its Role in HeredityFigure 11.7 Base Pairing in DNA Is Complementary
Chapter 11: DNA and Its Role in Heredity
Figure 11.8
Figure 11.8
figure 11-08.jpg
Chapter 11: DNA and Its Role in Heredity
DNA Replication
• Meselson and Stahl’s experiment (1957) proved replication of DNA to be semiconservative
• A parent strand is a template for synthesis of a new strand
• Two replicated DNA helices contain one parent strand and one synthesized strand each.
Chapter 11: DNA and Its Role in Heredity
Two Steps of DNA Replication
The DNA is denatured. New nucleotides are covalently bonded to the
each growing strand.
Chapter 11: DNA and Its Role in Heredity
The Mechanism of DNA Replication
• Nucleotides are always added to the growing 3’ end. Nucleotides are added by complementary base pairing with the template strand
• The free hydroxyl group reacts with one of the substrate’s phosphate groups, deoxyribonucleoside triphosphates, a bond breaks releasing two of the phosphate groups, releasing energy for DNA synthesis
• Review Figure 11.11
Chapter 11: DNA and Its Role in Heredity
Figure 11.11
Figure 11.11
figure 11-11.jpg
Chapter 11: DNA and Its Role in Heredity
The Mechanism of DNA Replication
• No DNA forms without a primer.• A primer is a short segment of DNA or RNA
that starts replication.• An enzyme, RNA primase, catalyzes the
synthesis of short RNA primers• Review Figure 11.15
Chapter 11: DNA and Its Role in Heredity
Figure 11.15
Figure 11.15
figure 11-15.jpg
Chapter 11: DNA and Its Role in Heredity
The Mechanism of DNA Replication
• DNA polymerase action causes the emerging leading strand to grow in the 5’-to-3’ direction.
• RNA primer is degraded and DNA replaces it.
Chapter 11: DNA and Its Role in Heredity
Many Proteins Assist in DNA Replication
• DNA helicases unwind the double helix, • Binding proteins keep the two strands
separated.• RNA primases makes the primer strand.• DNA polymerase adds nucleotides, proofreads
DNA and repairs it.• DNA ligase seals up breaks in the sugar-
phosphate backbone.
Chapter 11: DNA and Its Role in Heredity
Figure 11.16
Figure 11.16
figure 11-16.jpg
Chapter 11: DNA and Its Role in Heredity
Figure 11.17
Figure 11.17
figure 11-17.jpg
Chapter 11: DNA and Its Role in Heredity
The Mechanism of DNA Replication
• On the lagging strand, growing away from the replication fork, DNA is made in the 5’-to-3’ direction but synthesis is discontinuous: DNA is added as short fragments to primers, then the polymerase skips past the 5’ end to make the next fragment.
• Review Figures 11.16, 11.17 and 11.18
Chapter 11: DNA and Its Role in Heredity
Figure 11.18
Figure 11.18
figure 11-18.jpg
Chapter 11: DNA and Its Role in Heredity
Summary of DNA Replication
The replication begins at origins of replication - specific sequence of nucleotides which recognizes helicase.
Helicase unwinds the parental DNA. Single-strand binding proteins stabilize the
unwound parental DNA. Replication of DNA then proceeds in both
directions.
Chapter 11: DNA and Its Role in Heredity
Summary of DNA Replication
Primase joins RNA nucleotides to make a primer (~ 10 nucleotides long) to begin synthesis of the leading strand.
As nucleotides align with complementary bases along a template strand of DNA, they are added by polymerase, to the growing end of the new strand (50/second in human cells).
DNA polymerases add nucleotides only to the free 3’ end of the growing DNA strand.
Chapter 11: DNA and Its Role in Heredity
Summary of DNA Replication
The leading strand is synthesized continuously in the 5’ to 3’ direction by DNA polymerase.
The lagging strand is synthesized discontinously. Primase synthesizes short RNA primers to form Okazaki fragments.
The RNA primers are later replaced with DNA. DNA ligase joins the Okazaki fragment to the growing
strand.
Chapter 11: DNA and Its Role in Heredity
DNA Proofreading and Repair
• There is about about one error in 106 nucleotides bases added in DNA replication. That means about 1000 genes in every cell would be affected each time the cell divided.
• Errors are repaired by: proofreading, mismatch repair, and excision repair.
• Review Figure 11.19
Chapter 11: DNA and Its Role in Heredity
Proofreading Mechanism
DNA polymerase recognizes a typo, an extra base, deletes it and adds the correct base.
Synthesis continues
Chapter 11: DNA and Its Role in Heredity
Mismatch Repair Mechanism
The repair mechanism detects the “wrong” base before methylation has occurred.
Methyl groups (-CH3) are added to some cytosines.
Unmethylated strands are targeted for inspections.
A form of colon cancer arises from failure of mismatch repair.
Chapter 11: DNA and Its Role in Heredity
Excision Repair Mechanism
Removes abnormal bases due to chemical damages and replaces them with functional bases. (Example, skin cancer)
Enzymes inspect the cell’s DNA and cut the defective strand.
Another enzyme cuts away adjacent bases and the offending bases.
DNA polymerase synthesizes a new correct piece to replace the discarded one.
DNA ligase seals the new base in place.
Chapter 11: DNA and Its Role in Heredity
Figure 11.19
Figure 11.19
figure 11-19.jpg
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